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CPT 81457: Solid Organ Tumor Genomic Panel with MSI Analysis

CPT code 81457 represents a laboratory-based genomic sequence analysis panel for solid organ tumors that interrogates DNA sequence variants and assesses microsatellite instability (MSI). This molecular diagnostic service informs diagnosis, prognostication, and targeted therapy selection across a range of solid tumor malignancies and is increasingly central to precision oncology care nationwide. The code captures comprehensive DNA-based testing with an MSI component, distinguishing it from smaller targeted panels and larger comprehensive genomic profiles.

Key payers included in this analysis are Aetna, Blue Cross Blue Shield, Cigna Health, United Healthcare, and Medicare. Readers will find a concise overview of clinical context for use of 81457, how it relates to adjacent molecular pathology codes, and what typical sites of service and service types are associated with the code. The publication summarizes common billing and coding considerations, outlines typical clinical indications for tumor sequencing with MSI assessment, and highlights where 81457 fits in the landscape of molecular oncology testing (comparison to other CPT molecular panel codes). The goal is to provide health plan and provider stakeholders with a clear reference on the clinical purpose and coding identity of 81457, supporting consistent clinical documentation and coding practice at a national level.

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Billing Code Overview

CPT code 81457 describes a genomic sequence analysis panel performed on a patient tumor specimen to evaluate DNA sequence variants that impact diagnosis and treatment of solid organ cancers. The test also evaluates microsatellite instability (MSI), an indicator of genomic hypermutability that can influence therapeutic decision-making.

Service type: Laboratory-based tumor genomic sequencing with MSI analysis

Typical site of service: Clinical laboratory or hospital/medical center laboratory

National Reimbursement Benchmarks

Commercial national average pricing for CPT 81457 centers around BUCA’s mean of $769, with notable variation among major payers. Blue Cross Blue Shield’s median is relatively high at $807.90 while Aetna’s median sits at $663.00; Cigna and UnitedHealth Group have medians near $803.60 and $538.10 respectively. These central tendencies position BUCA’s average close to several large commercial payers, indicating the overall market hovers in the mid-to-high hundreds for this code.

Dispersion measured by the interquartile range (P75 minus P25) highlights where pricing spreads are tightest and widest: Blue Cross Blue Shield’s IQR is $395.40 (P75 $1,016.50 minus P25 $627.10), Cigna’s IQR is $595.20 (P75 $1,044.20 minus P25 $458.80), Aetna’s IQR is $330.90 (P75 $735.40 minus P25 $430.50), UnitedHealth Group’s IQR is $523.20 (P75 $896.90 minus P25 $376.70), and BUCA’s IQR is $308.70 (P75 $954.30 minus P25 $524.60). BUCA therefore shows the tightest quartile spread and Cigna the widest, with Blue Cross Blue Shield and UnitedHealth Group in between.

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CPT 81457: Solid Organ Tumor Genomic Panel with MSI Analysis

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Billing Code Overview

Service type: Laboratory-based tumor genomic sequencing with MSI analysis

Typical site of service: Clinical laboratory or hospital/medical center laboratory

National Reimbursement Benchmarks

National Payer Mean Reimbursement Rates

Clinical & Coding Specifications

Clinical Context

A 62-year-old patient with a newly diagnosed invasive adenocarcinoma of the rectum undergoes surgical resection. Tumor tissue is submitted to the pathology laboratory for molecular profiling to identify actionable DNA sequence variants and assess microsatellite instability (MSI) status to inform prognosis and targeted therapy selection. The clinical workflow begins with accessioning of the formalin-fixed paraffin-embedded (FFPE) tumor block by the pathology team. A pathologist reviews histology, marks tumor-rich areas, and estimates tumor cellularity. A molecular laboratory orders a genomic sequencing panel that interrogates multiple cancer-associated genes for single nucleotide variants, small insertions/deletions, and may include copy number assessment; MSI testing is performed either through sequencing-derived algorithms or adjunct testing. Results are analyzed by a molecular pathologist, who issues an integrated report describing clinically significant variants, MSI status, and potential therapeutic implications for the treating medical oncologist. Typical communications include a tumor board discussion involving the medical oncologist and surgical team. Billing for this service uses 81457 for solid tumor genomic panel testing that includes MSI assessment. Typical site of service is a hospital-based pathology/molecular laboratory or an independent clinical molecular laboratory. Typical patient scenario: adult with confirmed colorectal or small intestine malignancy (examples: C20, C18.0‑C19, C17.0‑C17.9) requiring comprehensive tumor profiling to guide adjuvant or systemic therapy selection.

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	Use when billing only the professional (interpretation) portion by a physician for the test result review and report.
`TC`	Technical component	Use when billing only the technical portion (laboratory processing, sequencing) of the test.
`90`	Reference (outside) lab	Use when the performing laboratory is different from the billing entity (test performed by an outside lab).
`62`	Two surgeons	Applicable rarely when a second surgeon provided distinct services related to specimen procurement that affects billing; used when specifically permitted.
`78`	Unplanned return to the operating room	Use when an unplanned reoperation leads to additional specimen collection or molecular testing tied to that event.
`80`	Assistant surgeon	Use if an assistant surgeon performed services affecting specimen acquisition and billing rules permit modifier application.
`52`	Reduced services	Use when the assay was partially performed or a limited panel was run versus the full service.
`53`	Discontinued service	Use when testing was started but discontinued for clinical/technical reasons prior to completion.
`22`	Increased procedural services	Use when work, time, or technical complexity substantially exceeds typical and documentation supports an increased charge.
`23`	Unusual anesthesia	Rarely applicable; use when unusual anesthesia circumstances affected specimen collection associated with the test.
`90`	Reference (outside) lab	Use when the performing lab is an independent reference lab — (listed again for emphasis when both components are split between entities).
`QK`	Clinical trial instance — physician	Use when specimen testing is performed as part of a clinical trial and the physician component is billed separately under trial reporting rules.
`QX`	Clinical trial instance — lab tech	Use when the laboratory technical component is associated with clinical trial research billing rules.
`QY`	Clinical trial instance — payer requirement	Use when a payer requires clinical trial modifier to identify investigational billing.

Taxonomy Code	Specialty	Notes
`207ZP0102X`	Pathology Physician	Typically orders, interprets, and signs molecular pathology reports for tumor profiling.
`207L00000X`	Anatomic Pathology & Clinical Pathology Physician	Dual-trained pathologists involved in histologic review and coordination of molecular testing.
`207RI0200X`	Medical Oncology Physician	Uses genomic and MSI results to guide systemic therapy selection and communicates findings to the patient.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`C17.0‑C17.9`	Malignant neoplasm of duodenum ‑ Malignant neoplasm of small intestine, unspecified	Small intestine cancers may require genomic profiling and MSI testing to guide systemic therapy and clinical trial eligibility.
`C18.0‑C19`	Malignant neoplasm of cecum ‑ Malignant neoplasm of rectosigmoid junction	Colonic tumors frequently undergo DNA-based panels and MSI testing to assess for mismatch repair deficiency and targeted therapy options.
`C20`	Malignant neoplasm of rectum	Rectal cancers are commonly profiled for actionable mutations and MSI status to inform neoadjuvant and adjuvant treatment.
`C21.1`	Malignant neoplasm of anal canal	Anal canal malignancies may undergo molecular testing when systemic therapy decisions or trial eligibility depend on genomic results.
`C21.2`	Malignant neoplasm of cloacogenic zone	Tumors in this region are included in colorectal/anal cancer profiling pathways requiring genomic and MSI assessment.
`C21.8`	Malignant neoplasm of overlapping sites of rectum, anus and anal canal	Overlapping-site tumors require profiling similar to rectal or anal primary tumors to guide therapy.
`C7A.020‑C7A.026`	Malignant carcinoid tumor of the appendix ‑ Malignant carcinoid tumor of the rectum	Neuroendocrine/neoplastic tumors of the appendix and rectum may be molecularly profiled when clinically indicated for treatment planning or trial enrollment.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`81445`	Targeted genomic sequence analysis panel (DNA‑based panels) for solid organ neoplasm testing	Smaller targeted DNA panels; may be ordered instead of or prior to `81457` when fewer genes are needed.
`81449`	RNA‑based targeted testing panel	Used when RNA fusion or expression testing is required in addition to DNA sequencing; can complement `81457`.
`81455`	Solid organ or hematolymphoid neoplasm genomic sequence analysis panel, ≥51 genes	Broader DNA-based panel option; overlaps with `81457` when gene content and variant types differ.
`81456`	Solid organ or hematolymphoid neoplasm genomic sequence analysis panel, ≥51 genes with RNA component	Comprehensive DNA+RNA panels that may be billed when RNA analysis is included beyond `81457` scope.
`81458`	Solid organ neoplasm genomic sequence analysis panel, interrogation for sequence variants with MSI and CNVs	Closely related — alternative code when MSI plus copy number variant interrogation is specifically reported.
`81459`	Comprehensive Genomic Profile (CGP) panel	Larger comprehensive profiling that may replace `81457` if criteria for CGP are met.
`81479`	Not Otherwise Classified (NOC) molecular pathology panel	Use when the performed panel does not meet definitions for listed molecular panel CPT codes including `81457`.

Related Codes

CPT-81410-GENOMIC-PANEL-AORTIC-DISEASE

CPT 81410: Genomic Sequencing Panel for Aortic Dysfunction

CPT-81411-GENETIC-DUPLICATION-DELETION-PANEL-AORTIC-DISEASE

CPT 81411: Genetic Duplication/Deletion Panel for Aortic Disease

CPT-81412-ASHKENAZI-JEWISH-GENOMIC-SEQUENCE-PANEL

CPT 81412: Ashkenazi Jewish Multi-Gene Genomic Sequence Panel

CPT-81413-GENOMIC-PANEL-CARDIAC-ION-CHANNELOPATHIES

CPT 81413: Genomic Panel for Cardiac Ion Channelopathies

CPT-81414-CARDIAC-ION-CHANNELOPATHY-CNV-PANEL

CPT 81414: Cardiac Ion Channelopathy CNV Panel

CPT-81415-EXOME-SEQUENCE-ANALYSIS-UNEXPLAINED-DISORDER

CPT 81415: Exome Sequence Analysis for Unexplained Disorders

CPT-81416-FAMILIAL-EXOME-SEQUENCE-ANALYSIS

CPT 81416: Familial Exome Sequence Analysis for Diagnostic Comparison

CPT-81417-EXOME-SEQUENCE-REEVALUATION

CPT 81417: Reanalysis of Existing Exome Sequence

CPT-81418-PHARMACOGENOMIC-MULTIGENE-DRUG-METABOLISM-PANEL

CPT 81418: Pharmacogenomic Multigene Drug-Metabolism Panel

CPT-81419-GENOMIC-SEQUENCE-PANEL-EPILEPSY

CPT 81419: Genomic Sequence Analysis Panel for Epilepsy

Showing 1–10 of 43

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 billing only the professional (interpretation) portion by a physician for the test result review and report.
`TC`	Technical component	Use when billing only the technical portion (laboratory processing, sequencing) of the test.
`90`	Reference (outside) lab	Use when the performing laboratory is different from the billing entity (test performed by an outside lab).
`62`	Two surgeons	Applicable rarely when a second surgeon provided distinct services related to specimen procurement that affects billing; used when specifically permitted.
`78`	Unplanned return to the operating room	Use when an unplanned reoperation leads to additional specimen collection or molecular testing tied to that event.
`80`	Assistant surgeon	Use if an assistant surgeon performed services affecting specimen acquisition and billing rules permit modifier application.
`52`	Reduced services	Use when the assay was partially performed or a limited panel was run versus the full service.
`53`	Discontinued service	Use when testing was started but discontinued for clinical/technical reasons prior to completion.
`22`	Increased procedural services	Use when work, time, or technical complexity substantially exceeds typical and documentation supports an increased charge.
`23`	Unusual anesthesia	Rarely applicable; use when unusual anesthesia circumstances affected specimen collection associated with the test.
`90`	Reference (outside) lab	Use when the performing lab is an independent reference lab — (listed again for emphasis when both components are split between entities).
`QK`	Clinical trial instance — physician	Use when specimen testing is performed as part of a clinical trial and the physician component is billed separately under trial reporting rules.
`QX`	Clinical trial instance — lab tech	Use when the laboratory technical component is associated with clinical trial research billing rules.
`QY`	Clinical trial instance — payer requirement	Use when a payer requires clinical trial modifier to identify investigational billing.

Taxonomy Code	Specialty	Notes
`207ZP0102X`	Pathology Physician	Typically orders, interprets, and signs molecular pathology reports for tumor profiling.
`207L00000X`	Anatomic Pathology & Clinical Pathology Physician	Dual-trained pathologists involved in histologic review and coordination of molecular testing.
`207RI0200X`	Medical Oncology Physician	Uses genomic and MSI results to guide systemic therapy selection and communicates findings to the patient.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`C17.0‑C17.9`	Malignant neoplasm of duodenum ‑ Malignant neoplasm of small intestine, unspecified	Small intestine cancers may require genomic profiling and MSI testing to guide systemic therapy and clinical trial eligibility.
`C18.0‑C19`	Malignant neoplasm of cecum ‑ Malignant neoplasm of rectosigmoid junction	Colonic tumors frequently undergo DNA-based panels and MSI testing to assess for mismatch repair deficiency and targeted therapy options.
`C20`	Malignant neoplasm of rectum	Rectal cancers are commonly profiled for actionable mutations and MSI status to inform neoadjuvant and adjuvant treatment.
`C21.1`	Malignant neoplasm of anal canal	Anal canal malignancies may undergo molecular testing when systemic therapy decisions or trial eligibility depend on genomic results.
`C21.2`	Malignant neoplasm of cloacogenic zone	Tumors in this region are included in colorectal/anal cancer profiling pathways requiring genomic and MSI assessment.
`C21.8`	Malignant neoplasm of overlapping sites of rectum, anus and anal canal	Overlapping-site tumors require profiling similar to rectal or anal primary tumors to guide therapy.
`C7A.020‑C7A.026`	Malignant carcinoid tumor of the appendix ‑ Malignant carcinoid tumor of the rectum	Neuroendocrine/neoplastic tumors of the appendix and rectum may be molecularly profiled when clinically indicated for treatment planning or trial enrollment.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`81445`	Targeted genomic sequence analysis panel (DNA‑based panels) for solid organ neoplasm testing	Smaller targeted DNA panels; may be ordered instead of or prior to `81457` when fewer genes are needed.
`81449`	RNA‑based targeted testing panel	Used when RNA fusion or expression testing is required in addition to DNA sequencing; can complement `81457`.
`81455`	Solid organ or hematolymphoid neoplasm genomic sequence analysis panel, ≥51 genes	Broader DNA-based panel option; overlaps with `81457` when gene content and variant types differ.
`81456`	Solid organ or hematolymphoid neoplasm genomic sequence analysis panel, ≥51 genes with RNA component	Comprehensive DNA+RNA panels that may be billed when RNA analysis is included beyond `81457` scope.
`81458`	Solid organ neoplasm genomic sequence analysis panel, interrogation for sequence variants with MSI and CNVs	Closely related — alternative code when MSI plus copy number variant interrogation is specifically reported.
`81459`	Comprehensive Genomic Profile (CGP) panel	Larger comprehensive profiling that may replace `81457` if criteria for CGP are met.
`81479`	Not Otherwise Classified (NOC) molecular pathology panel	Use when the performed panel does not meet definitions for listed molecular panel CPT codes including `81457`.

Related Codes

CPT-81410-GENOMIC-PANEL-AORTIC-DISEASE

CPT 81410: Genomic Sequencing Panel for Aortic Dysfunction

CPT-81411-GENETIC-DUPLICATION-DELETION-PANEL-AORTIC-DISEASE

CPT 81411: Genetic Duplication/Deletion Panel for Aortic Disease

CPT-81412-ASHKENAZI-JEWISH-GENOMIC-SEQUENCE-PANEL

CPT 81412: Ashkenazi Jewish Multi-Gene Genomic Sequence Panel

CPT-81413-GENOMIC-PANEL-CARDIAC-ION-CHANNELOPATHIES

CPT 81413: Genomic Panel for Cardiac Ion Channelopathies

CPT-81414-CARDIAC-ION-CHANNELOPATHY-CNV-PANEL

CPT 81414: Cardiac Ion Channelopathy CNV Panel

CPT-81415-EXOME-SEQUENCE-ANALYSIS-UNEXPLAINED-DISORDER

CPT 81415: Exome Sequence Analysis for Unexplained Disorders

CPT-81416-FAMILIAL-EXOME-SEQUENCE-ANALYSIS

CPT 81416: Familial Exome Sequence Analysis for Diagnostic Comparison

CPT-81417-EXOME-SEQUENCE-REEVALUATION

CPT 81417: Reanalysis of Existing Exome Sequence

CPT-81418-PHARMACOGENOMIC-MULTIGENE-DRUG-METABOLISM-PANEL

CPT 81418: Pharmacogenomic Multigene Drug-Metabolism Panel

CPT-81419-GENOMIC-SEQUENCE-PANEL-EPILEPSY

CPT 81419: Genomic Sequence Analysis Panel for Epilepsy

Showing 1–10 of 43

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.