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CPT 81518: mRNA 11-Gene Expression Profiling for Metastatic Recurrence Risk

CPT code 81518 covers an mRNA-based molecular diagnostic assay that profiles 11 genes and uses an algorithmic analysis of lab results and patient data to generate a percentage risk of metastatic recurrence and to assess possible benefit from extended endocrine therapy. This test is clinically significant for guiding adjuvant therapy decisions in patients where recurrence risk and extended endocrine treatment benefit are uncertain. Nationally, such assays influence oncology care pathways, therapy selection, and downstream follow-up strategies.

Key payers in the coverage landscape include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. The publication provides a national perspective on coverage contours and typical billing considerations for this category of genomic testing.

Readers will find benchmarks and contextual clinical information about the assay’s role in treatment planning, common sites of service and laboratory settings, and an outline of typical billing and coding considerations associated with algorithm-based molecular diagnostics. The report also summarizes payer coverage patterns and policy themes relevant to reimbursement and utilization oversight for prognostic gene-expression assays. Data not available in the input is noted where specific payer policy details, associated taxonomies, ICD-10 pairings, and related codes would normally be listed.

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Billing Code Overview

CPT code 81518 describes a laboratory service that performs mRNA gene expression profiling of 11 genes and applies an algorithmic analysis combining patient data and lab results to report a percentage risk for metastatic recurrence and to evaluate the potential benefit of extended endocrine therapy. The analysis is a molecular diagnostics assay that produces a prognostic risk score to inform endocrine treatment decisions.

Service type: Molecular diagnostic laboratory test with algorithm-based risk reporting
Typical site of service: Clinical laboratory or pathology laboratory performing high-complexity molecular testing

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CPT 81518: mRNA 11-Gene Expression Profiling for Metastatic Recurrence Risk

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Get alerted when payer policies referencing 81518 are released or updated.

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Billing Code Overview

Service type: Molecular diagnostic laboratory test with algorithm-based risk reporting
Typical site of service: Clinical laboratory or pathology laboratory performing high-complexity molecular testing

Clinical & Coding Specifications

Clinical Context

A 58-year-old woman with early-stage, hormone receptor–positive, HER2-negative invasive breast carcinoma undergoes surgical resection. Pathology reports confirm node-negative disease with a tumor size of 1.8 cm and intermediate histologic grade. The oncology team orders genomic risk stratification to inform adjuvant systemic therapy decisions, specifically to estimate 10-year risk of distant (metastatic) recurrence and to evaluate possible benefit from extended endocrine therapy. A lab technician in a CLIA-certified molecular diagnostics laboratory performs 81518 testing: extracting RNA from the tumor specimen, running mRNA expression profiling for the specified 11 genes, and executing the proprietary algorithm that combines patient clinical variables and assay results to generate a numeric percentage risk for metastatic recurrence and a report regarding extended endocrine therapy benefit. The result is transmitted to the ordering medical oncologist, who integrates the report with clinical and pathologic factors during a follow-up visit to finalize adjuvant treatment planning.

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	Use when billing only the professional/interpretive component of a test if separate from technical processing.
`TC`	Technical component	Use when billing only the technical component (laboratory processing, instrumentation) separate from professional interpretation.
`90`	Reference (outside) laboratory	Use when the service is performed by an outside laboratory and results are reported by the billing provider.
`91`	Repeat clinical diagnostic laboratory test (Not listed in raw modifiers)	Data not available in the input.
`52`	Reduced services	Use when the test is partially reduced or incomplete due to specimen quality or partial processing.
`53`	Discontinued procedure	Use if testing was started but discontinued for patient-related or specimen-related reasons.
`59`	Distinct procedural service (Not listed in raw modifiers)	Data not available in the input.
`90`	Duplicate entry handled above	Duplicate entry — already listed.
`90`	Duplicate entries are not allowed — please refer to listed modifiers.	Duplicate handling.

Taxonomy Code	Specialty	Notes
208000000X	Medical Oncology	Ordering clinicians who interpret genomic recurrence risk to guide systemic therapy decisions.
207RC0000X	Clinical Molecular Genetics	Specialists involved in molecular testing design and interpretation.
208000000P	Hematology/Oncology (combined)	Physicians who coordinate adjuvant systemic treatment and survivorship planning.
2083P0200X	Surgical Oncology	Surgeons who may order tests post-resection to assist with adjuvant planning.
363L00000X	Laboratory – Molecular Pathology	Laboratory professionals performing the assay and algorithmic analysis.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`C50.911`	Malignant neoplasm of unspecified site of right female breast	Primary diagnosis for which gene expression profiling with `81518` is commonly used to estimate recurrence risk.
`C50.912`	Malignant neoplasm of unspecified site of left female breast	Same clinical context for left-sided invasive breast carcinoma guiding adjuvant therapy decisions.
`C50.919`	Malignant neoplasm of unspecified site of unspecified female breast	Used when laterality is not specified in documentation; still relevant for recurrence risk testing.
`Z85.3`	Personal history of malignant neoplasm of breast	May appear in follow-up patients assessing risk of recurrence or considering extended endocrine therapy.
`D05.91`	Unspecified type of intraductal carcinoma in situ of breast	In select clinical scenarios, genomic tests may be considered in DCIS-to-invasive risk discussions, though primary indication remains invasive carcinoma.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`88305`	Level IV surgical pathology, gross and microscopic examination	Performed on the tumor specimen to provide histopathologic staging and tumor characteristics that complement `81518` molecular risk assessment.
`88342`	Immunohistochemistry, per single antibody stain	May be used to determine hormone receptor (ER/PR) and HER2 status that are clinical variables incorporated into adjuvant decisions alongside `81518`.
`81210`	BRCA1 and BRCA2 analysis (sequence analysis)	Performed in selected patients for hereditary risk assessment; separate from tumor mRNA profiling but part of comprehensive oncologic evaluation.
`84999`	Unlisted chemistry procedure	May be used rarely for novel or proprietary lab components ancillary to the main assay when no specific code applies.
`99000`	Handling and/or conveyance of body fluid specimen	Administrative/ancillary code related to specimen transport; supportive to the technical performance of `81518`.

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

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.

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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.

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Clinical & Coding Specifications

Clinical Context

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	Use when billing only the professional/interpretive component of a test if separate from technical processing.
`TC`	Technical component	Use when billing only the technical component (laboratory processing, instrumentation) separate from professional interpretation.
`90`	Reference (outside) laboratory	Use when the service is performed by an outside laboratory and results are reported by the billing provider.
`91`	Repeat clinical diagnostic laboratory test (Not listed in raw modifiers)	Data not available in the input.
`52`	Reduced services	Use when the test is partially reduced or incomplete due to specimen quality or partial processing.
`53`	Discontinued procedure	Use if testing was started but discontinued for patient-related or specimen-related reasons.
`59`	Distinct procedural service (Not listed in raw modifiers)	Data not available in the input.
`90`	Duplicate entry handled above	Duplicate entry — already listed.
`90`	Duplicate entries are not allowed — please refer to listed modifiers.	Duplicate handling.

Taxonomy Code	Specialty	Notes
208000000X	Medical Oncology	Ordering clinicians who interpret genomic recurrence risk to guide systemic therapy decisions.
207RC0000X	Clinical Molecular Genetics	Specialists involved in molecular testing design and interpretation.
208000000P	Hematology/Oncology (combined)	Physicians who coordinate adjuvant systemic treatment and survivorship planning.
2083P0200X	Surgical Oncology	Surgeons who may order tests post-resection to assist with adjuvant planning.
363L00000X	Laboratory – Molecular Pathology	Laboratory professionals performing the assay and algorithmic analysis.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`C50.911`	Malignant neoplasm of unspecified site of right female breast	Primary diagnosis for which gene expression profiling with `81518` is commonly used to estimate recurrence risk.
`C50.912`	Malignant neoplasm of unspecified site of left female breast	Same clinical context for left-sided invasive breast carcinoma guiding adjuvant therapy decisions.
`C50.919`	Malignant neoplasm of unspecified site of unspecified female breast	Used when laterality is not specified in documentation; still relevant for recurrence risk testing.
`Z85.3`	Personal history of malignant neoplasm of breast	May appear in follow-up patients assessing risk of recurrence or considering extended endocrine therapy.
`D05.91`	Unspecified type of intraductal carcinoma in situ of breast	In select clinical scenarios, genomic tests may be considered in DCIS-to-invasive risk discussions, though primary indication remains invasive carcinoma.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`88305`	Level IV surgical pathology, gross and microscopic examination	Performed on the tumor specimen to provide histopathologic staging and tumor characteristics that complement `81518` molecular risk assessment.
`88342`	Immunohistochemistry, per single antibody stain	May be used to determine hormone receptor (ER/PR) and HER2 status that are clinical variables incorporated into adjuvant decisions alongside `81518`.
`81210`	BRCA1 and BRCA2 analysis (sequence analysis)	Performed in selected patients for hereditary risk assessment; separate from tumor mRNA profiling but part of comprehensive oncologic evaluation.
`84999`	Unlisted chemistry procedure	May be used rarely for novel or proprietary lab components ancillary to the main assay when no specific code applies.
`99000`	Handling and/or conveyance of body fluid specimen	Administrative/ancillary code related to specimen transport; supportive to the technical performance of `81518`.

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

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 81518: mRNA 11-Gene Expression Profiling for Metastatic Recurrence Risk

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Billing Code Overview

OpenPayer

CPT 81518: mRNA 11-Gene Expression Profiling for Metastatic Recurrence Risk

Sign up for cpt 81518 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