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CPT 81528: Stool DNA and Fecal Hemoglobin Colorectal Cancer Screening Test

CPT code 81528 represents a stool-based colorectal cancer screening assay that combines fecal hemoglobin testing with real-time amplification of multiple DNA markers and an algorithmic interpretation to report a positive or negative result. This molecular and immunochemical diagnostic service matters nationally because it supports noninvasive screening, can increase screening uptake, and has implications for early detection pathways and downstream diagnostic workflows.

Key payers examined in coverage and reimbursement discussions include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. The analysis addresses how major payers classify and reimburse advanced stool-based tests, where coverage policies and prior authorization requirements may affect access, and how Medicare policy frameworks influence national uptake.

Readers will find benchmarks on coding and payer coverage, a concise clinical context for interpreting the test's role in screening strategies, and summaries of policy considerations that affect utilization and billing. The report highlights typical use cases, site-of-service implications for clinical laboratories and reference labs, and areas where payers' policy language may differ. Data not available in the input is noted where specific payer policy details or utilization metrics are absent.

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Billing Code Overview

CPT code 81528 describes a laboratory service that analyzes a stool sample for colorectal cancer screening. The test includes technical laboratory assays for fecal hemoglobin and real-time amplification of 10 DNA markers, followed by an algorithmic analysis combining patient data and laboratory results to report a positive or negative screening outcome.

Service type: Laboratory molecular and immunochemical diagnostic testing with algorithmic interpretation
Typical site of service: Clinical laboratory or reference laboratory performing stool-based colorectal cancer screening tests

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CPT 81528: Stool DNA and Fecal Hemoglobin Colorectal Cancer Screening Test

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Billing Code Overview

Service type: Laboratory molecular and immunochemical diagnostic testing with algorithmic interpretation
Typical site of service: Clinical laboratory or reference laboratory performing stool-based colorectal cancer screening tests

Clinical & Coding Specifications

Clinical Context

A 58-year-old average-risk adult receives a commercially available stool-based colorectal cancer screening kit by mail. The patient collects a single stool specimen at home and returns it to a central laboratory. The laboratory performs a fecal hemoglobin immunoassay and real-time molecular amplification targeting a panel of 10 DNA markers associated with colorectal neoplasia. A laboratory technologist runs the analytic instruments, processes controls, and then executes a validated algorithm that integrates the molecular results, fecal hemoglobin level, and limited patient data (age, sex, prior screening history) to generate a single binary report: positive (requires diagnostic colonoscopy) or negative (routine screening interval). Typical workflow steps: kit accessioning, specimen integrity check, fecal hemoglobin assay, nucleic acid extraction and amplification, quality control review, algorithmic result generation, and final result reporting to the ordering clinician or screening program. Typical site of service is an independent clinical laboratory or hospital-based laboratory performing high-complexity molecular diagnostics. Typical patient scenario: screening of adults aged 45–75 for colorectal cancer who prefer non-invasive home testing or who missed colonoscopy; results guide need for diagnostic colonoscopy or routine surveillance.

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	Use when reporting only the professional component (interpretation or physician component) if separate from the laboratory technical work.
`TC`	Technical component	Use when billing only the technical component of the test performed by the laboratory.
`90`	Reference (outside) laboratory	Use when the service was performed by an outside reference laboratory and only reporting entity bills.
`59`	Distinct procedural service	Use when a separate, distinct service is furnished on the same date that is not ordinarily bundled with the test (use sparingly and with documentation).
`52`	Reduced services	Use when the laboratory performed a reduced service compared to full procedure (document reason and extent).
`53`	Discontinued procedure	Use when testing was started but discontinued for documented clinical reasons prior to completion.
`90`	(duplicate entry avoided)	(See above)
`AS`	Collaborative or assistant surgeon (context-specific)	Rarely applicable; not typical for lab-based tests but present in modifier set — generally not used for this service.
`QK`	Medical direction of two, three, or four technicians/assistants	Not typically used for lab assays; included in modifier list but seldom applicable.
`QX`	Service furnished under a physician assistant/advanced practice clinician's supervision	Use when applicable billing rules require identification of non-physician practitioner involvement in reporting.
`QY`	Medical direction of one physician by another	Use only if applicable to the ordering or supervising physician relationship under specific payor rules.
`GA`	Waiver of liability statement issued, voluntary under payer policy	Use when a signed ABN-like waiver applies per payer when services may be non-covered.
`CO`	Charge exempt (workers' compensation)	Use when the claim is subject to a workers' compensation payer and exempt from certain charges.
`TG`	Acquired/processed specimen from a deceased individual	Use only when specimen originates from a deceased donor; rarely applicable for screening tests.

Taxonomy Code	Specialty	Notes
207Q00000X	Clinical Laboratory	Typical for high-complexity molecular laboratories performing the assay and technical reporting.
208M00000X	Pathology	Pathologists may provide medical direction, review quality control, and sign out results.
207L00000X	Diagnostic Molecular Laboratory	Specialty focused on molecular diagnostic testing and assay validation.
363A00000X	Laboratory Director (Clinical)	Physicians or PhDs serving as laboratory directors overseeing compliance and results interpretation.
363LF0000X	Laboratory Manager	Operational oversight of specimen flow and technical staff in the lab.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`Z12.11`	Encounter for screening for malignant neoplasm of colon	Primary screening indication for stool-based colorectal cancer tests in asymptomatic adults.
`Z80.0`	Family history of malignant neoplasm of digestive organs	Family history may prompt screening discussions and use of noninvasive tests when colonoscopy deferred.
`K52.9`	Noninfective gastroenteritis and colitis, unspecified	Symptoms or GI conditions that may affect stool test interpretation or prompt alternative diagnostic evaluation.
`R19.7`	Diarrhea, unspecified	Altered bowel habit can affect specimen quality and timing of stool collection; may lead to repeat testing.
`R19.5`	Other fecal abnormalities	Abnormal stool characteristics that may impact test validity and require clinical correlation.
`Z86.010`	Personal history of colonic polyps	Prior polyps increase surveillance intensity; stool-based testing may be part of follow-up strategies for some patients.
`Z85.038`	Personal history of malignant neoplasm of large intestine	Past colorectal cancer history informs screening modality selection and follow-up after noninvasive testing.
`R63.5`	Abnormal weight gain	General clinical context note; less directly related but can appear in preventive care visits where screening is ordered.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`81528`	Fecal hemoglobin and amplification of 10 DNA markers with algorithmic analysis; report positive/negative	Primary laboratory assay and algorithmic interpretation described; this is the core billed service for the stool-based colorectal cancer screening test.
`82270`	Blood, occult, feces by immunoassay, qualitative	Alternative or adjunct fecal immunochemical test (FIT) sometimes performed in screening programs; may be used in different testing strategies or prior testing.
`81325`	BRAF (v-raf murine sarcoma viral oncogene homolog B1) gene analysis, if specifically performed	Example molecular code for a targeted DNA analysis; included as a representative molecular companion test in workflows that may expand biomarker panels.
`G0105`	Colorectal cancer screening; colonoscopy on individual at high risk	Downstream diagnostic procedure triggered by a positive stool-based screening test.
`G0121`	Colorectal cancer screening; colonoscopy, screening, average risk	Downstream diagnostic or screening colonoscopy performed after positive noninvasive test or as primary screening alternative.
`88305`	Surgical pathology, gross and microscopic examination	If diagnostic colonoscopy leads to biopsy, pathology codes like this are used for tissue evaluation.

Note: The 81528 code is the index code for the described stool-based molecular and fecal hemoglobin screening test; listed related CPTs represent common follow-up tests or alternative screening modalities used in clinical workflows.

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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Clinical & Coding Specifications

Clinical Context

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	Use when reporting only the professional component (interpretation or physician component) if separate from the laboratory technical work.
`TC`	Technical component	Use when billing only the technical component of the test performed by the laboratory.
`90`	Reference (outside) laboratory	Use when the service was performed by an outside reference laboratory and only reporting entity bills.
`59`	Distinct procedural service	Use when a separate, distinct service is furnished on the same date that is not ordinarily bundled with the test (use sparingly and with documentation).
`52`	Reduced services	Use when the laboratory performed a reduced service compared to full procedure (document reason and extent).
`53`	Discontinued procedure	Use when testing was started but discontinued for documented clinical reasons prior to completion.
`90`	(duplicate entry avoided)	(See above)
`AS`	Collaborative or assistant surgeon (context-specific)	Rarely applicable; not typical for lab-based tests but present in modifier set — generally not used for this service.
`QK`	Medical direction of two, three, or four technicians/assistants	Not typically used for lab assays; included in modifier list but seldom applicable.
`QX`	Service furnished under a physician assistant/advanced practice clinician's supervision	Use when applicable billing rules require identification of non-physician practitioner involvement in reporting.
`QY`	Medical direction of one physician by another	Use only if applicable to the ordering or supervising physician relationship under specific payor rules.
`GA`	Waiver of liability statement issued, voluntary under payer policy	Use when a signed ABN-like waiver applies per payer when services may be non-covered.
`CO`	Charge exempt (workers' compensation)	Use when the claim is subject to a workers' compensation payer and exempt from certain charges.
`TG`	Acquired/processed specimen from a deceased individual	Use only when specimen originates from a deceased donor; rarely applicable for screening tests.

Taxonomy Code	Specialty	Notes
207Q00000X	Clinical Laboratory	Typical for high-complexity molecular laboratories performing the assay and technical reporting.
208M00000X	Pathology	Pathologists may provide medical direction, review quality control, and sign out results.
207L00000X	Diagnostic Molecular Laboratory	Specialty focused on molecular diagnostic testing and assay validation.
363A00000X	Laboratory Director (Clinical)	Physicians or PhDs serving as laboratory directors overseeing compliance and results interpretation.
363LF0000X	Laboratory Manager	Operational oversight of specimen flow and technical staff in the lab.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`Z12.11`	Encounter for screening for malignant neoplasm of colon	Primary screening indication for stool-based colorectal cancer tests in asymptomatic adults.
`Z80.0`	Family history of malignant neoplasm of digestive organs	Family history may prompt screening discussions and use of noninvasive tests when colonoscopy deferred.
`K52.9`	Noninfective gastroenteritis and colitis, unspecified	Symptoms or GI conditions that may affect stool test interpretation or prompt alternative diagnostic evaluation.
`R19.7`	Diarrhea, unspecified	Altered bowel habit can affect specimen quality and timing of stool collection; may lead to repeat testing.
`R19.5`	Other fecal abnormalities	Abnormal stool characteristics that may impact test validity and require clinical correlation.
`Z86.010`	Personal history of colonic polyps	Prior polyps increase surveillance intensity; stool-based testing may be part of follow-up strategies for some patients.
`Z85.038`	Personal history of malignant neoplasm of large intestine	Past colorectal cancer history informs screening modality selection and follow-up after noninvasive testing.
`R63.5`	Abnormal weight gain	General clinical context note; less directly related but can appear in preventive care visits where screening is ordered.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`81528`	Fecal hemoglobin and amplification of 10 DNA markers with algorithmic analysis; report positive/negative	Primary laboratory assay and algorithmic interpretation described; this is the core billed service for the stool-based colorectal cancer screening test.
`82270`	Blood, occult, feces by immunoassay, qualitative	Alternative or adjunct fecal immunochemical test (FIT) sometimes performed in screening programs; may be used in different testing strategies or prior testing.
`81325`	BRAF (v-raf murine sarcoma viral oncogene homolog B1) gene analysis, if specifically performed	Example molecular code for a targeted DNA analysis; included as a representative molecular companion test in workflows that may expand biomarker panels.
`G0105`	Colorectal cancer screening; colonoscopy on individual at high risk	Downstream diagnostic procedure triggered by a positive stool-based screening test.
`G0121`	Colorectal cancer screening; colonoscopy, screening, average risk	Downstream diagnostic or screening colonoscopy performed after positive noninvasive test or as primary screening alternative.
`88305`	Surgical pathology, gross and microscopic examination	If diagnostic colonoscopy leads to biopsy, pathology codes like this are used for tissue evaluation.

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.

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CPT 81528: Stool DNA and Fecal Hemoglobin Colorectal Cancer Screening Test

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Billing Code Overview

OpenPayer

CPT 81528: Stool DNA and Fecal Hemoglobin Colorectal Cancer Screening Test

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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