Find policies, billing codes, payers, states, and providers

CPT 81529: mRNA Expression Profiling for Melanoma Recurrence Risk

CPT code 81529 represents a laboratory-developed molecular diagnostic assay that quantifies mRNA expression of 31 genes from FFPE melanoma tumor tissue and applies an algorithm to report a risk score for recurrence and the likelihood of sentinel lymph node metastasis. This code matters nationally because it supports clinical decision-making about surveillance and surgical management for cutaneous melanoma by providing prognostic information beyond traditional histopathology. Payers commonly reviewing coverage for this test include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare.

Readers will find benchmarks and guidance on the clinical context for use of this assay, an overview of payer coverage considerations, and the operational implications for laboratories and ordering clinicians. The content summarizes what the code represents, typical sites of service, and the clinical purpose—risk stratification for melanoma recurrence and sentinel node metastasis probability. Where available, the publication will cover reimbursement benchmarks, coding and billing considerations, and relevant policy trends that may affect access to molecular prognostic testing for cutaneous melanoma. Data not available in the input is noted as such in specific sections.

Customize your policy alerts

Sign up for cpt 81529 policy alerts

Get alerted when payer policies referencing 81529 are released or updated.

Monitor payer policy activity

Receive email alerts as soon as relevant payer policies are published or updated.

Billing Code Overview

CPT code 81529 describes a laboratory diagnostic assay performed on a formalin–fixed paraffin–embedded (FFPE) tumor tissue specimen to measure mRNA expression of 31 genes (28 content genes and 3 housekeeping genes). The test includes both the technical laboratory analysis of the FFPE specimen and an algorithmic computation that combines test results with patient data to generate a risk score for cutaneous melanoma recurrence, including the likelihood of sentinel lymph node metastasis.

Service type: Laboratory molecular diagnostic test with algorithmic risk modeling
Typical site of service: Clinical molecular diagnostics laboratory (specimen collected at outpatient or hospital setting; testing performed in a reference or hospital lab)

Explore openpayer tools

View all tools

Find policies, billing codes, payers, states, and providers

CPT 81529: mRNA Expression Profiling for Melanoma Recurrence Risk

Customize your policy alerts

Sign up for cpt 81529 policy alerts

Get alerted when payer policies referencing 81529 are released or updated.

Monitor payer policy activity

Receive email alerts as soon as relevant payer policies are published or updated.

Billing Code Overview

Service type: Laboratory molecular diagnostic test with algorithmic risk modeling
Typical site of service: Clinical molecular diagnostics laboratory (specimen collected at outpatient or hospital setting; testing performed in a reference or hospital lab)

Clinical & Coding Specifications

Clinical Context

A 58-year-old patient presents with a newly diagnosed cutaneous melanoma after wide local excision of a suspicious pigmented lesion. The surgical pathology report on formalin–fixed paraffin–embedded (FFPE) tumor tissue confirms invasive melanoma and requests prognostic molecular testing to refine recurrence risk and sentinel lymph node involvement probability. The specimen block is sent to an external clinical molecular laboratory. A histology technician prepares unstained FFPE sections; a molecular technologist performs mRNA extraction and a validated 31-gene expression assay. A laboratory analyst carries out the technical assay and runs the algorithmic analysis incorporating the assay results and available clinicopathologic data to generate a continuous and categorical risk score for melanoma recurrence and estimated likelihood of sentinel lymph node metastasis. Results are reported to the ordering dermatologist, surgical oncologist or medical oncologist and become part of the medical record to inform surveillance intensity and consideration of staging or adjuvant therapy. Typical sites of service include hospital-based pathology laboratories, independent clinical molecular laboratories, and outpatient reference laboratories that receive FFPE surgical pathology specimens.

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	Append when reporting only the professional (interpretive) component if applicable for split billing; for lab-only molecular tests this is rarely used but applies when a pathologist provides separate interpretation.
`TC`	Technical component	Use when billing only the technical component (laboratory processing and analytic work) performed by the lab.
`90`	Reference (outside) laboratory	Use when the performing laboratory bills but the specimen was collected elsewhere or the test was sent out to a reference lab.
`91`	Repeat clinical diagnostic laboratory test (non-standard here)	Data not in provided modifiers list; excluded.
`59`	Distinct procedural service	Data not in provided modifiers list; excluded.
`52`	Reduced services	Use when the lab performed an abbreviated or partial version of the assay due to insufficient specimen or quality, resulting in reduced reimbursement.
`53`	Discontinued procedure	Use if testing was started but discontinued for technical reasons (e.g., failed extraction, degraded RNA) and documentation supports termination.
`76`	Repeat procedure by same physician	Data not in provided modifiers list; excluded.
`77`	Repeat procedure by another physician	Data not in provided modifiers list; excluded.
`80`	Assistant surgeon	Use when a qualified assistant (e.g., pathologist assistant) provides a billable component under appropriate circumstances; rarely applicable for specialized molecular testing.
`82`	Assistant surgeon (when qualified resident not available)	Rarely applicable; use only per payer policy when an assistant is required and no resident is available.
`62`	Two surgeons	Generally not applicable; included when dual surgical participation affects related surgical claims.
`78`	Unplanned return to the operating room	Not typically applicable to the lab test but included when related operative care requires re-intervention.
`11`	Certification/authorization: Not standard CMS modifier for cert	Included in raw list but not a standard CMS billing modifier for services; exclude clinical use.
`22`	Increased procedural services	Use when the laboratory documents and justifies substantially greater work or complexity for the assay beyond typical expectations (rare).

Taxonomy Code	Specialty	Notes
`207K00000X`	Dermatopathology	Dermatopathologists frequently order, interpret, and correlate molecular prognostic tests for cutaneous melanoma.
`207L00000X`	Anatomic Pathology	Anatomic pathologists oversee specimen processing and may sign out reports that incorporate molecular results.
`363LP0800X`	Clinical Laboratory Molecular Pathology	Molecular pathologists and lab directors supervise and validate mRNA expression assays and algorithmic reporting.
`208D00000X`	Dermatology	Dermatologists commonly order molecular prognostic tests after excision to inform management.
`207P00000X`	Surgical Pathology	Surgical pathologists manage FFPE tissue submission and correlate molecular findings with histopathology.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`C43.9`	Malignant melanoma of skin, unspecified	Primary diagnosis for patients undergoing tumor prognostic profiling to assess recurrence risk.
`C43.2`	Malignant melanoma of skin of trunk	Common anatomic site for melanoma specimens submitted for mRNA expression prognostic testing.
`C43.5`	Malignant melanoma of skin of lower limb, including hip	Melanomas from extremities frequently require staging and prognostic evaluation with molecular assays.
`C43.4`	Malignant melanoma of skin of scalp and neck	Head and neck melanomas have distinct prognostic implications; molecular risk scores support management decisions.
`D03.9`	Melanoma in situ, unspecified	In selected cases, ambiguous in situ lesions may prompt molecular tests when invasive potential is uncertain.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`88305`	Level IV surgical pathology, gross and microscopic examination	Often reported by pathology for initial histologic evaluation of the excised melanoma specimen that provides tissue for the molecular test.
`88313`	Immunohistochemistry, per specimen; first single antibody stain	Used when IHC stains (e.g., S100, SOX10, Melan-A) are performed to confirm melanocytic origin before or alongside molecular prognostic testing.
`88342`	Histopathology consultative rendering, professional consultation	May be used when an outside dermatopathologist provides consultative review that informs molecular testing decisions.
`0000F`	(Not a valid CPT code)	Data not available in the input.
`99000`	Handling and/or conveyance of specimen (historical ancillary)	Not a standard CPT molecular code; specimen handling is typically bundled—but listed here to reflect ancillary specimen logistics when billed by some facilities.

CPT 81490: RA Disease Activity Score from 12-Serum Biomarker Panel

CPT-81493-CORONARY-ARTERY-DISEASE-23-GENE-RT-PCR-RISK-SCORE

CPT 81493: 23-Gene RT-PCR Test with Algorithmic CAD Risk Score

CPT-81500-CA125-HE4-ALGORITHMIC-RISK-SCORE

CPT 81500: CA-125 and HE4 Laboratory Testing with Algorithmic Risk Score

CPT-81503-ALGORITHMIC-LAB-RISK-SCORE-CA125-APOLIPOPROTEIN-A1

CPT 81503: Algorithmic Laboratory Risk Score Using Multiple Biomarkers

CPT-81504-TUMOR-ORIGIN-RNA-EXPRESSION-CLASSIFIER

CPT 81504: RNA Expression Tumor Origin Classifier

CPT-81506-DIABETES-BIOMARKER-PANEL-WITH-RISK-SCORE

CPT 81506: Diabetes Biomarker Panel with Algorithmic Risk Score

CPT-81507-NIPS-CELL-FREE-DNA-TRISOMY-RISK-ANALYSIS

CPT 81507: Non-Invasive Prenatal Screening for Trisomies 13, 18, 21

CPT-81508-PAPP-A-HCG-ALGORITHMIC-RISK-ASSAY

CPT 81508: PAPP–A and hCG Laboratory Assay with Algorithmic Risk Score

CPT-81509-LAB-ALGORITHMIC-RISK-ASSESSMENT-PAPP-A-HCG-DIA

CPT 81509: Laboratory Algorithmic Risk Assessment for PAPP–A, hCG, DIA

CPT-81510-PRENATAL-TRIPLE-MARKER-ALGORITHMIC-RISK-ASSESSMENT

CPT 81510: Prenatal Triple-Analyte Algorithmic Risk Assessment

Showing 1–10 of 41

Frequently Asked Questions

References

1.CPT® Codes and Descriptions. AAPC. Retrieved Aug 11, 2026.Maintains the CPT code set's official descriptions and guidelines, licensed from the American Medical Association, used as the definitional source for CPT codes on this page.
2.HCPCS Quarterly Update. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's quarterly release of HCPCS Level II codes and short/long descriptors, the source for HCPCS code definitions and update history.
3.ICD-10-CM Full Code List. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's complete ICD-10-CM diagnosis code list, used to cross-reference diagnosis codes associated with this procedure or service.

Published by

Trek Health powers OpenPayer with a leading commercial payer intelligence platform, seamlessly converting fragmented payer data into actionable insights for provider organizations.

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Explore openpayer tools

View all tools

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	Append when reporting only the professional (interpretive) component if applicable for split billing; for lab-only molecular tests this is rarely used but applies when a pathologist provides separate interpretation.
`TC`	Technical component	Use when billing only the technical component (laboratory processing and analytic work) performed by the lab.
`90`	Reference (outside) laboratory	Use when the performing laboratory bills but the specimen was collected elsewhere or the test was sent out to a reference lab.
`91`	Repeat clinical diagnostic laboratory test (non-standard here)	Data not in provided modifiers list; excluded.
`59`	Distinct procedural service	Data not in provided modifiers list; excluded.
`52`	Reduced services	Use when the lab performed an abbreviated or partial version of the assay due to insufficient specimen or quality, resulting in reduced reimbursement.
`53`	Discontinued procedure	Use if testing was started but discontinued for technical reasons (e.g., failed extraction, degraded RNA) and documentation supports termination.
`76`	Repeat procedure by same physician	Data not in provided modifiers list; excluded.
`77`	Repeat procedure by another physician	Data not in provided modifiers list; excluded.
`80`	Assistant surgeon	Use when a qualified assistant (e.g., pathologist assistant) provides a billable component under appropriate circumstances; rarely applicable for specialized molecular testing.
`82`	Assistant surgeon (when qualified resident not available)	Rarely applicable; use only per payer policy when an assistant is required and no resident is available.
`62`	Two surgeons	Generally not applicable; included when dual surgical participation affects related surgical claims.
`78`	Unplanned return to the operating room	Not typically applicable to the lab test but included when related operative care requires re-intervention.
`11`	Certification/authorization: Not standard CMS modifier for cert	Included in raw list but not a standard CMS billing modifier for services; exclude clinical use.
`22`	Increased procedural services	Use when the laboratory documents and justifies substantially greater work or complexity for the assay beyond typical expectations (rare).

Taxonomy Code	Specialty	Notes
`207K00000X`	Dermatopathology	Dermatopathologists frequently order, interpret, and correlate molecular prognostic tests for cutaneous melanoma.
`207L00000X`	Anatomic Pathology	Anatomic pathologists oversee specimen processing and may sign out reports that incorporate molecular results.
`363LP0800X`	Clinical Laboratory Molecular Pathology	Molecular pathologists and lab directors supervise and validate mRNA expression assays and algorithmic reporting.
`208D00000X`	Dermatology	Dermatologists commonly order molecular prognostic tests after excision to inform management.
`207P00000X`	Surgical Pathology	Surgical pathologists manage FFPE tissue submission and correlate molecular findings with histopathology.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`C43.9`	Malignant melanoma of skin, unspecified	Primary diagnosis for patients undergoing tumor prognostic profiling to assess recurrence risk.
`C43.2`	Malignant melanoma of skin of trunk	Common anatomic site for melanoma specimens submitted for mRNA expression prognostic testing.
`C43.5`	Malignant melanoma of skin of lower limb, including hip	Melanomas from extremities frequently require staging and prognostic evaluation with molecular assays.
`C43.4`	Malignant melanoma of skin of scalp and neck	Head and neck melanomas have distinct prognostic implications; molecular risk scores support management decisions.
`D03.9`	Melanoma in situ, unspecified	In selected cases, ambiguous in situ lesions may prompt molecular tests when invasive potential is uncertain.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`88305`	Level IV surgical pathology, gross and microscopic examination	Often reported by pathology for initial histologic evaluation of the excised melanoma specimen that provides tissue for the molecular test.
`88313`	Immunohistochemistry, per specimen; first single antibody stain	Used when IHC stains (e.g., S100, SOX10, Melan-A) are performed to confirm melanocytic origin before or alongside molecular prognostic testing.
`88342`	Histopathology consultative rendering, professional consultation	May be used when an outside dermatopathologist provides consultative review that informs molecular testing decisions.
`0000F`	(Not a valid CPT code)	Data not available in the input.
`99000`	Handling and/or conveyance of specimen (historical ancillary)	Not a standard CPT molecular code; specimen handling is typically bundled—but listed here to reflect ancillary specimen logistics when billed by some facilities.

CPT 81490: RA Disease Activity Score from 12-Serum Biomarker Panel

CPT-81493-CORONARY-ARTERY-DISEASE-23-GENE-RT-PCR-RISK-SCORE

CPT 81493: 23-Gene RT-PCR Test with Algorithmic CAD Risk Score

CPT-81500-CA125-HE4-ALGORITHMIC-RISK-SCORE

CPT 81500: CA-125 and HE4 Laboratory Testing with Algorithmic Risk Score

CPT-81503-ALGORITHMIC-LAB-RISK-SCORE-CA125-APOLIPOPROTEIN-A1

CPT 81503: Algorithmic Laboratory Risk Score Using Multiple Biomarkers

CPT-81504-TUMOR-ORIGIN-RNA-EXPRESSION-CLASSIFIER

CPT 81504: RNA Expression Tumor Origin Classifier

CPT-81506-DIABETES-BIOMARKER-PANEL-WITH-RISK-SCORE

CPT 81506: Diabetes Biomarker Panel with Algorithmic Risk Score

CPT-81507-NIPS-CELL-FREE-DNA-TRISOMY-RISK-ANALYSIS

CPT 81507: Non-Invasive Prenatal Screening for Trisomies 13, 18, 21

CPT-81508-PAPP-A-HCG-ALGORITHMIC-RISK-ASSAY

CPT 81508: PAPP–A and hCG Laboratory Assay with Algorithmic Risk Score

CPT-81509-LAB-ALGORITHMIC-RISK-ASSESSMENT-PAPP-A-HCG-DIA

CPT 81509: Laboratory Algorithmic Risk Assessment for PAPP–A, hCG, DIA

CPT-81510-PRENATAL-TRIPLE-MARKER-ALGORITHMIC-RISK-ASSESSMENT

CPT 81510: Prenatal Triple-Analyte Algorithmic Risk Assessment

Showing 1–10 of 41

Frequently Asked Questions

References

1.CPT® Codes and Descriptions. AAPC. Retrieved Aug 11, 2026.Maintains the CPT code set's official descriptions and guidelines, licensed from the American Medical Association, used as the definitional source for CPT codes on this page.
2.HCPCS Quarterly Update. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's quarterly release of HCPCS Level II codes and short/long descriptors, the source for HCPCS code definitions and update history.
3.ICD-10-CM Full Code List. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's complete ICD-10-CM diagnosis code list, used to cross-reference diagnosis codes associated with this procedure or service.

Published by

Trek Health powers OpenPayer with a leading commercial payer intelligence platform, seamlessly converting fragmented payer data into actionable insights for provider organizations.

OpenPayer

CPT 81529: mRNA Expression Profiling for Melanoma Recurrence Risk

Sign up for cpt 81529 policy alerts

Billing Code Overview

OpenPayer

CPT 81529: mRNA Expression Profiling for Melanoma Recurrence Risk

Sign up for cpt 81529 policy alerts

Billing Code Overview

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Related Diagnoses

Related CPT Codes

Related Codes

References

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Related Diagnoses

Related CPT Codes

Related Codes

References

CPT 81529: mRNA Expression Profiling for Melanoma Recurrence Risk

Sign up for cpt 81529 policy alerts

Billing Code Overview

CPT 81529: mRNA Expression Profiling for Melanoma Recurrence Risk

Sign up for cpt 81529 policy alerts

Billing Code Overview

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Related Diagnoses

Related CPT Codes

Related Codes

What does CPT 81529 represent and what does the service include?

Where is the test performed and how is the specimen handled for billing?

Which CPT modifiers are relevant when billing CPT 81529?

What other CPT codes are typically associated with the pathology and specimen workflow for this assay?

Which diagnosis codes are relevant when ordering CPT 81529?

References

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Related Diagnoses

Related CPT Codes

Related Codes

What does CPT 81529 represent and what does the service include?

Where is the test performed and how is the specimen handled for billing?

Which CPT modifiers are relevant when billing CPT 81529?

What other CPT codes are typically associated with the pathology and specimen workflow for this assay?

Which diagnosis codes are relevant when ordering CPT 81529?

References