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

CPT code 81500 covers a lab-based service that combines assays for CA-125 and HE4 with an algorithmic analysis of patient data to produce a patient-specific risk score. This molecular/biomarker testing with algorithmic interpretation supports clinical decision-making in assessing disease risk, and its use has implications for diagnostic pathways, care coordination, and laboratory workflows nationwide.

Key payers included in the national analysis are Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find a concise overview of the clinical context for CA-125 and HE4 biomarker testing, national reimbursement benchmarks where available, coding and billing considerations for a laboratory performing both the technical assays and algorithmic reporting, and the policy landscape influencing coverage for algorithm-based diagnostic tests. The publication outlines operational implications for clinical laboratories and diagnostic facilities and highlights areas where payer policies and coding practices intersect with clinical use of algorithmic risk scores.

Data not available in the input for specific reimbursement rates, associated taxonomies, or ICD-10 diagnosis mappings is noted where applicable.

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Billing Code Overview

CPT code 81500 describes a laboratory service in which the lab analyst performs the technical assays for CA-125 and HE4 and applies an algorithmic analysis to combine those test results with patient data to generate and report a patient risk score. The service type is laboratory molecular/biomarker testing with algorithmic risk assessment. The typical site of service is a clinical laboratory or diagnostic testing facility, where specimen processing, assay performance, and computational analysis are completed and the resulting risk score is reported to the ordering clinician.

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

Data not available in the input for specific reimbursement rates, associated taxonomies, or ICD-10 diagnosis mappings is noted where applicable.

Customize your policy alerts

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Get alerted when payer policies referencing 81500 are released or updated.

Monitor payer policy activity

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Billing Code Overview

Clinical & Coding Specifications

Clinical Context

A 56-year-old woman with a pelvic mass and abnormal transvaginal ultrasound is seen in a gynecologic oncology clinic to evaluate risk for epithelial ovarian cancer. Her clinician orders serum biomarker testing for CA-125 and HE4, and sends the sample to a reference laboratory that performs the technical assays and applies an FDA-cleared algorithm combining the two markers with patient age and menopausal status to generate a numerical risk score. The laboratory analyst receives the specimen, performs immunoassays for CA-125 and HE4, verifies quality controls, enters patient demographic variables, runs the risk‑prediction algorithm, documents the technical results and algorithm output, and reports the patient risk score to the ordering provider via the laboratory information system. Results inform shared decision-making about further imaging, referral to gynecologic oncology, or surgical planning.

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	Use when billing only the professional interpretation component by the physician when applicable (rare for purely technical lab tests).
`TC`	Technical component	Use when billing only the technical component of the laboratory testing and algorithm processing.
`90`	Reference (outside) laboratory	Use when specimen processing or testing is performed by an outside reference laboratory.
`91`	Repeat clinical diagnostic laboratory test	Not in provided list; excluded.
`52`	Reduced services	Use when the laboratory performs a reduced level of service compared with the full procedure.
`53`	Discontinued procedure	Use when specimen collection or analysis was started but discontinued for documented clinical reasons.
`59`	Distinct procedural service	Not in provided list; excluded.
`QK`	Medical direction of certified assistants	Use when the physician billed for medical direction of two or more assistants (rare in lab setting).
`QX`	Services performed by an auxiliary under qualified supervision	Use when portions of testing are performed by an auxiliary under direct supervision consistent with local rules.
`QY`	Attending physician not medically directing	Use when physician supervision arrangements meet the `QY` definition (varies by payer).
`90`	Reference (outside) laboratory	(Duplicate entry avoided in table - only one instance should be used.)
`22`	Increased procedural services	Use when unusually high complexity of processing or algorithm validation increases resource use.
`52`	Reduced services	(Duplicate entry avoided in table - only one instance should be used.)

Taxonomy Code	Specialty	Notes
362500000X	Clinical Pathology	Physicians overseeing laboratory testing, validation, and result interpretation.
207P00000X	Obstetrics & Gynecology	Ordering clinicians who evaluate adnexal masses and interpret risk scores in clinical context.
363L00000X	Clinical Laboratory Scientist	Laboratory professionals performing the assays and algorithmic analysis.
207RX0400X	Gynecologic Oncology	Specialists who use the risk score to guide surgical planning and referral.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`C56.9`	Malignant neoplasm of ovary, unspecified	Ovarian cancer is a primary indication for using `CA-125` and `HE4` biomarker panels and risk algorithms.
`N83.2`	Torsion of ovary, ovarian pedicle	Adnexal masses with torsion can present with elevated tumor markers; risk assessment may influence urgency and surgical planning.
`N83.20`	Ovarian torsion, unspecified ovary	See above; included as a related adnexal emergency where evaluation of malignancy risk may occur.
`N83.9`	Noninflammatory disorder of ovary, fallopian tube and broad ligament, unspecified	Benign ovarian masses are common and differentiation from malignant lesions is the clinical question addressed by the test.
`R19.8`	Other specified symptoms and signs involving the digestive system and abdomen	Nonspecific abdominal symptoms prompting pelvic imaging and biomarker testing to evaluate adnexal pathology.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`81500`	CA-125 and HE4 algorithmic analysis to report patient risk score (technical lab testing and algorithm)	Primary code describing the laboratory assay and algorithmic risk score generated from `CA-125` and `HE4`.
`86304`	Immunoassay for tumor antigen, quantitative; multiple analytes (e.g., CA-125)	Common laboratory method to measure `CA-125` values that feed into the algorithm; may be billed by the performing lab.
`86255`	Immunoassay for tumor marker, quantitative; cancer antigen 125 (CA-125)	Direct assay code often used for the individual `CA-125` analyte measurement when reported separately.
`86301`	Immunoassay for tumor antigen, quantitative; single analyte (e.g., HE4)	Method-level code for measuring `HE4` when billed separately from the algorithmic report.
`99000`	Handling and/or conveyance of specimen	Administrative/handling codes used by some laboratories for specimen processing and transportation (payer-specific).

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-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

CPT-81511-MULTIANALYTE-SERUM-SCREENING-ALGORITHMIC-RISK-SCORE

CPT 81511: Multianalyte Serum Screening with Algorithmic Risk Score

Showing 1–10 of 41

Frequently Asked Questions

References

1.CPT® Codes and Descriptions. AAPC. Retrieved Jul 29, 2026.
2.HCPCS Quarterly Update. Centers for Medicare & Medicaid Services (CMS). Retrieved Jul 29, 2026.
3.ICD-10-CM Full Code List. Centers for Medicare & Medicaid Services (CMS). Retrieved Jul 29, 2026.

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.

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	Use when billing only the professional interpretation component by the physician when applicable (rare for purely technical lab tests).
`TC`	Technical component	Use when billing only the technical component of the laboratory testing and algorithm processing.
`90`	Reference (outside) laboratory	Use when specimen processing or testing is performed by an outside reference laboratory.
`91`	Repeat clinical diagnostic laboratory test	Not in provided list; excluded.
`52`	Reduced services	Use when the laboratory performs a reduced level of service compared with the full procedure.
`53`	Discontinued procedure	Use when specimen collection or analysis was started but discontinued for documented clinical reasons.
`59`	Distinct procedural service	Not in provided list; excluded.
`QK`	Medical direction of certified assistants	Use when the physician billed for medical direction of two or more assistants (rare in lab setting).
`QX`	Services performed by an auxiliary under qualified supervision	Use when portions of testing are performed by an auxiliary under direct supervision consistent with local rules.
`QY`	Attending physician not medically directing	Use when physician supervision arrangements meet the `QY` definition (varies by payer).
`90`	Reference (outside) laboratory	(Duplicate entry avoided in table - only one instance should be used.)
`22`	Increased procedural services	Use when unusually high complexity of processing or algorithm validation increases resource use.
`52`	Reduced services	(Duplicate entry avoided in table - only one instance should be used.)

Taxonomy Code	Specialty	Notes
362500000X	Clinical Pathology	Physicians overseeing laboratory testing, validation, and result interpretation.
207P00000X	Obstetrics & Gynecology	Ordering clinicians who evaluate adnexal masses and interpret risk scores in clinical context.
363L00000X	Clinical Laboratory Scientist	Laboratory professionals performing the assays and algorithmic analysis.
207RX0400X	Gynecologic Oncology	Specialists who use the risk score to guide surgical planning and referral.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`C56.9`	Malignant neoplasm of ovary, unspecified	Ovarian cancer is a primary indication for using `CA-125` and `HE4` biomarker panels and risk algorithms.
`N83.2`	Torsion of ovary, ovarian pedicle	Adnexal masses with torsion can present with elevated tumor markers; risk assessment may influence urgency and surgical planning.
`N83.20`	Ovarian torsion, unspecified ovary	See above; included as a related adnexal emergency where evaluation of malignancy risk may occur.
`N83.9`	Noninflammatory disorder of ovary, fallopian tube and broad ligament, unspecified	Benign ovarian masses are common and differentiation from malignant lesions is the clinical question addressed by the test.
`R19.8`	Other specified symptoms and signs involving the digestive system and abdomen	Nonspecific abdominal symptoms prompting pelvic imaging and biomarker testing to evaluate adnexal pathology.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`81500`	CA-125 and HE4 algorithmic analysis to report patient risk score (technical lab testing and algorithm)	Primary code describing the laboratory assay and algorithmic risk score generated from `CA-125` and `HE4`.
`86304`	Immunoassay for tumor antigen, quantitative; multiple analytes (e.g., CA-125)	Common laboratory method to measure `CA-125` values that feed into the algorithm; may be billed by the performing lab.
`86255`	Immunoassay for tumor marker, quantitative; cancer antigen 125 (CA-125)	Direct assay code often used for the individual `CA-125` analyte measurement when reported separately.
`86301`	Immunoassay for tumor antigen, quantitative; single analyte (e.g., HE4)	Method-level code for measuring `HE4` when billed separately from the algorithmic report.
`99000`	Handling and/or conveyance of specimen	Administrative/handling codes used by some laboratories for specimen processing and transportation (payer-specific).

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-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

CPT-81511-MULTIANALYTE-SERUM-SCREENING-ALGORITHMIC-RISK-SCORE

CPT 81511: Multianalyte Serum Screening with Algorithmic Risk Score

Showing 1–10 of 41

Frequently Asked Questions

References

1.CPT® Codes and Descriptions. AAPC. Retrieved Jul 29, 2026.
2.HCPCS Quarterly Update. Centers for Medicare & Medicaid Services (CMS). Retrieved Jul 29, 2026.
3.ICD-10-CM Full Code List. Centers for Medicare & Medicaid Services (CMS). Retrieved Jul 29, 2026.

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

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Billing Code Overview

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OpenPayer

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

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

Sign up for cpt 81500 policy alerts

Billing Code Overview

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

Sign up for cpt 81500 policy alerts

Billing Code Overview

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Related Diagnoses

Related CPT Codes

Related Codes

What does CPT 81500 cover and where is this service typically performed?

Which CPT modifiers are listed for use with CPT 81500?

What other CPT codes are associated with the assays and reporting in CPT 81500?

In what clinical scenarios is the CA‑125/HE4 algorithmic risk score typically used?

Which payers were included in the national analysis, and does the page provide reimbursement rates?

References

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Related Diagnoses

Related CPT Codes

Related Codes

What does CPT 81500 cover and where is this service typically performed?

Which CPT modifiers are listed for use with CPT 81500?

What other CPT codes are associated with the assays and reporting in CPT 81500?

In what clinical scenarios is the CA‑125/HE4 algorithmic risk score typically used?

Which payers were included in the national analysis, and does the page provide reimbursement rates?

References