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CPT 81520: mRNA 58-Gene Breast Cancer Recurrence Score Test

CPT code 81520 represents a high-complexity molecular diagnostic test: mRNA gene expression profiling of 58 genes using hybrid capture, with an algorithmic analysis that produces a breast cancer recurrence score. Nationally, this code captures services used to guide prognostic assessment and therapeutic decision-making for breast cancer patients, where genomic test results inform recurrence risk estimation and potential treatment pathways. Its use reflects the growing role of genomic assays in oncology care and reimbursement policy discussions.

Key payers covered in this analysis include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find a concise overview of the clinical purpose of the test, typical laboratory settings where the test is performed, and the payer landscape addressed. The publication outlines benchmarks relevant to coverage and utilization, summarizes recent policy and coding guidance affecting molecular diagnostic claims, and provides clinical context on how a recurrence score derived from gene expression profiling is used in breast cancer management.

The content is intended for national audiences including payers, laboratory managers, coding and billing professionals, and oncology clinicians seeking a clear summary of CPT code 81520 and its implications for service coding and policy.

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Billing Code Overview

CPT code 81520 describes laboratory testing that performs mRNA gene expression profiling for 58 genes using hybrid capture and applies an algorithmic analysis that integrates patient data with the laboratory results to produce a breast cancer recurrence score. The service type is molecular pathology / genomic diagnostic testing, focused on gene expression profiling. The typical site of service is a clinical molecular diagnostics laboratory or other specialized laboratory setting where high-complexity molecular testing is performed.

Data not available in the input.

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CPT 81520: mRNA 58-Gene Breast Cancer Recurrence Score Test

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Get alerted when payer policies referencing 81520 are released or updated.

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Billing Code Overview

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Clinical & Coding Specifications

Clinical Context

A 52-year-old woman with newly diagnosed, early-stage, hormone receptor–positive, HER2-negative invasive breast carcinoma undergoes breast-conserving surgery. Final pathology reports a tumor size of 2.1 cm, grade II, with 0–1 positive sentinel lymph node(s). The treating medical oncologist orders a genomic assay to inform adjuvant systemic therapy decisions. A tissue specimen (formalin-fixed paraffin-embedded tumor block) is sent to a molecular diagnostics laboratory. In the lab, a molecular technologist extracts RNA, performs hybrid capture-based mRNA gene expression profiling of a 58-gene panel, and the laboratory information system combines the technical assay results with the patient’s clinicopathologic data to generate an algorithmic breast cancer recurrence score. The laboratory issues a report used by the oncologist to guide recommendations about chemotherapy versus endocrine therapy. Typical site of service is a CLIA-certified reference molecular pathology laboratory or hospital-based molecular diagnostic laboratory; specimens are collected in the hospital, outpatient surgical center, or physician office and shipped to the reference lab.

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	Use when only the professional/interpretive component of a test is billed by a physician or pathologist separate from the technical component.
`TC`	Technical component	Use when billing only the technical component (laboratory testing) performed by the lab.
`90`	Reference laboratory	Use when the service is performed by an outside (reference) laboratory different from the billing provider.
`QK`	CLIA waived specimen collection supervision	Rarely used; apply when specific Medicare rules require documenting supervision of waived tests (not typical for this molecular assay).
`QX`	Qualified nonphysician practitioner	Use when a qualified nonphysician provider performed an action tied to the service and payer requires the modifier.
`QY`	Attending provider is a resident — primary care exception	Use per payer rules when a teaching physician/resident relationship affects billing (rare in reference lab tests).
`90`	Reference laboratory	(Listed once above; if a payer requires single use, apply as specified.)
`22`	Increased procedural services	Use when the laboratory documents unusually high complexity or work beyond the usual for analytic processing or complex troubleshooting (rare and requires justification).
`52`	Reduced services	Use when the test is partially performed and a reduced service is billable (e.g., insufficient specimen prevents full panel).
`53`	Discontinued procedure	Use if testing was started but discontinued due to catastrophic specimen failure.
`59`*	Distinct procedural service	Data not available in the input.
`62`	Two surgeons	Not applicable to lab-only services; included among common modifiers but typically not used for this CPT.

Taxonomy Code	Specialty	Notes
207Q00000X	Anatomic Pathology	Pathologists interpret tumor pathology and may oversee molecular testing.
2085P0200X	Molecular Pathology	Laboratory molecular pathologists or molecular diagnostic specialists supervise and interpret assays.
363L00000X	Laboratory Director	Clinical laboratory directors or medical laboratory scientists oversee technical testing and quality.
207K00000X	Hematology & Oncology	Medical oncologists order the assay and use the recurrence score to guide systemic therapy.
208VP0000X	Surgical Pathology	Surgical pathologists handle specimen accessioning and histologic correlation.

*Note: 59 was not in the provided modifier list; it is shown here as unavailable per strict rules and should not be used. Data not available in the input.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`C50.912`	Malignant neoplasm of unspecified site of right female breast	Common primary diagnosis indicating invasive breast cancer for which recurrence risk profiling is appropriate.
`C50.911`	Malignant neoplasm of unspecified site of left female breast	As above for left-sided tumors; test guides adjuvant treatment decisions.
`C50.919`	Malignant neoplasm of unspecified breast, unspecified laterality	Used when laterality unspecified; still indicates invasive breast cancer eligible for recurrence score testing.
`D05.90`	Unspecified diagnosis of ductal carcinoma in situ of the breast	Some non-invasive cases may be considered for genomic assays in select scenarios; typically less common for this specific 58-gene recurrence score.
`Z85.3`	Personal history of malignant neoplasm of breast	May appear in patient history and influence risk assessment and testing decisions.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`88305`	Level IV surgical pathology, gross and microscopic examination	Performed on the excised tumor specimen before molecular testing to provide histologic diagnosis and tumor content assessment required for assay eligibility.
`88172`	Cytopathology; diagnostic evaluation of fine needle aspiration (presence/absence of malignancy)	If a core or FNA sample is used for initial diagnosis, cytopathology codes capture preliminary cellular evaluation prior to molecular assay selection.
`88342`	Immunohistochemistry, each antibody (e.g., ER/PR/HER2)	Performed to determine hormone receptor and HER2 status that inform assay appropriateness and are integrated into clinical decision-making.
`81301`	Molecular pathology procedure, e.g., gene-specific mutation analysis (example code)	Other molecular tests performed on the specimen (mutation testing) may be ordered in parallel depending on clinical need; used when separate targeted molecular analyses are performed.
`99000`	Handling and/or special specimen processing (example ancillary code)	Ancillary specimen handling or special shipping/preparation charges that some payers allow in coordination with reference lab testing.

If additional related CPT codes were provided in the input, they would be listed here. Data not available in the input.

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 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 only the professional/interpretive component of a test is billed by a physician or pathologist separate from the technical component.
`TC`	Technical component	Use when billing only the technical component (laboratory testing) performed by the lab.
`90`	Reference laboratory	Use when the service is performed by an outside (reference) laboratory different from the billing provider.
`QK`	CLIA waived specimen collection supervision	Rarely used; apply when specific Medicare rules require documenting supervision of waived tests (not typical for this molecular assay).
`QX`	Qualified nonphysician practitioner	Use when a qualified nonphysician provider performed an action tied to the service and payer requires the modifier.
`QY`	Attending provider is a resident — primary care exception	Use per payer rules when a teaching physician/resident relationship affects billing (rare in reference lab tests).
`90`	Reference laboratory	(Listed once above; if a payer requires single use, apply as specified.)
`22`	Increased procedural services	Use when the laboratory documents unusually high complexity or work beyond the usual for analytic processing or complex troubleshooting (rare and requires justification).
`52`	Reduced services	Use when the test is partially performed and a reduced service is billable (e.g., insufficient specimen prevents full panel).
`53`	Discontinued procedure	Use if testing was started but discontinued due to catastrophic specimen failure.
`59`*	Distinct procedural service	Data not available in the input.
`62`	Two surgeons	Not applicable to lab-only services; included among common modifiers but typically not used for this CPT.

Taxonomy Code	Specialty	Notes
207Q00000X	Anatomic Pathology	Pathologists interpret tumor pathology and may oversee molecular testing.
2085P0200X	Molecular Pathology	Laboratory molecular pathologists or molecular diagnostic specialists supervise and interpret assays.
363L00000X	Laboratory Director	Clinical laboratory directors or medical laboratory scientists oversee technical testing and quality.
207K00000X	Hematology & Oncology	Medical oncologists order the assay and use the recurrence score to guide systemic therapy.
208VP0000X	Surgical Pathology	Surgical pathologists handle specimen accessioning and histologic correlation.

*Note: 59 was not in the provided modifier list; it is shown here as unavailable per strict rules and should not be used. Data not available in the input.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`C50.912`	Malignant neoplasm of unspecified site of right female breast	Common primary diagnosis indicating invasive breast cancer for which recurrence risk profiling is appropriate.
`C50.911`	Malignant neoplasm of unspecified site of left female breast	As above for left-sided tumors; test guides adjuvant treatment decisions.
`C50.919`	Malignant neoplasm of unspecified breast, unspecified laterality	Used when laterality unspecified; still indicates invasive breast cancer eligible for recurrence score testing.
`D05.90`	Unspecified diagnosis of ductal carcinoma in situ of the breast	Some non-invasive cases may be considered for genomic assays in select scenarios; typically less common for this specific 58-gene recurrence score.
`Z85.3`	Personal history of malignant neoplasm of breast	May appear in patient history and influence risk assessment and testing decisions.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`88305`	Level IV surgical pathology, gross and microscopic examination	Performed on the excised tumor specimen before molecular testing to provide histologic diagnosis and tumor content assessment required for assay eligibility.
`88172`	Cytopathology; diagnostic evaluation of fine needle aspiration (presence/absence of malignancy)	If a core or FNA sample is used for initial diagnosis, cytopathology codes capture preliminary cellular evaluation prior to molecular assay selection.
`88342`	Immunohistochemistry, each antibody (e.g., ER/PR/HER2)	Performed to determine hormone receptor and HER2 status that inform assay appropriateness and are integrated into clinical decision-making.
`81301`	Molecular pathology procedure, e.g., gene-specific mutation analysis (example code)	Other molecular tests performed on the specimen (mutation testing) may be ordered in parallel depending on clinical need; used when separate targeted molecular analyses are performed.
`99000`	Handling and/or special specimen processing (example ancillary code)	Ancillary specimen handling or special shipping/preparation charges that some payers allow in coordination with reference lab testing.

If additional related CPT codes were provided in the input, they would be listed here. Data not available in the input.

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 81520: mRNA 58-Gene Breast Cancer Recurrence Score Test

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Billing Code Overview

OpenPayer

CPT 81520: mRNA 58-Gene Breast Cancer Recurrence Score Test

Sign up for cpt 81520 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