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CPT 81459: Tumor Genomic Sequencing Panel for Solid Organ Cancers

CPT code 81459 denotes a comprehensive genomic sequencing panel for solid tumor specimens that evaluates DNA and RNA variants, copy number changes, and rearrangements, and reports clinically relevant biomarkers such as microsatellite instability (MSI) and tumor mutation burden (TMB). This test informs diagnostic classification and treatment selection in oncology, including targeted therapies and immunotherapy decisions, and therefore holds growing national importance as precision oncology expands.

Key payers in the analysis include Aetna, Blue Cross Blue Shield, Cigna Health, United Healthcare, and Medicare. Readers will find a concise overview of clinical context, common sites of service, and payer coverage considerations. The publication summarizes how CPT code 81459 is used to bill large-panel tumor profiling services, contrasts it with unlisted molecular pathology coding, and highlights common billing modifiers and associated service lines where provided.

This briefing is designed to help billing managers, laboratory directors, and policy analysts understand the clinical scope of CPT code 81459, typical implementation settings, and the payer landscape relevant to nationwide practice. Data not available in the input are identified where applicable.

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Billing Code Overview

CPT code 81459 describes a comprehensive genomic sequencing panel performed on a patient tumor specimen to evaluate DNA and RNA sequence variants, copy number variants, and rearrangements that can affect diagnosis and treatment of solid organ cancers. The analysis also assesses additional tumor characteristics that may guide therapy selection, including microsatellite instability (MSI) and tumor mutation burden (TMB).

Service type: Comprehensive genomic sequencing / tumor profiling panel

Typical site of service: Clinical molecular pathology laboratory or hospital-based molecular diagnostics laboratory, with specimen collection typically occurring in oncology clinics or hospital outpatient settings.

National Reimbursement Benchmarks

Commercial national benchmarks for CPT 81459 center around BUCA’s average commercial rate of $2,433.30, with individual plans showing varied central tendency and dispersion. Blue Cross Blue Shield’s median sits near BUCA’s midpoint but its distribution is wide; Cigna and Aetna have relatively high medians and means, while UnitedHealth Group shows a lower median versus its mean, indicating some high outliers driving the average upward.

Assessing dispersion using the interquartile range (P75 minus P25) highlights differences in consistency: Blue Cross Blue Shield has the widest IQR at $1,442.60, followed by Cigna at $1,952.40 and BUCA at $1,485.30. The tightest spread is Aetna at $897.60, with UnitedHealth Group showing a moderate IQR of $1,733.90. These spreads reflect which payers have more concentrated commercial rates versus those with broader variability.

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CPT 81459: Tumor Genomic Sequencing Panel for Solid Organ Cancers

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Billing Code Overview

Service type: Comprehensive genomic sequencing / tumor profiling panel

National Reimbursement Benchmarks

National Payer Mean Reimbursement Rates

Clinical & Coding Specifications

Clinical Context

A patient with a newly diagnosed or recurrent solid organ malignancy undergoes comprehensive genomic profiling of a tumor specimen to identify clinically actionable DNA and RNA alterations. Typical scenario: a 62-year-old patient with metastatic non-small cell lung carcinoma has tumor biopsy submitted to a reference molecular laboratory for a broad next-generation sequencing panel that assesses single nucleotide variants, small insertions/deletions, copy number variants, gene rearrangements, microsatellite instability (MSI), and tumor mutational burden (TMB). The clinical workflow begins with the ordering clinician (medical oncologist or surgeon) entering the test order in the electronic medical record with ICD-10 diagnosis Z15.89 (genetic susceptibility to other disease) or the encounter/screening code Z13.79 if obtained as part of a screening/assessment. The pathology team accession the specimen, perform histologic confirmation and macrodissection as needed, and send extracted nucleic acid to the molecular laboratory. The laboratory performs library preparation, next-generation sequencing, bioinformatic analysis, and interpretation. Results are returned to the ordering clinician and incorporated into treatment planning, such as selection of targeted therapies or immunotherapy based on identified variants, MSI, or elevated TMB. Common sites of service include hospital outpatient departments, freestanding reference laboratories, and academic medical center pathology labs handling tumor specimens from biopsies, surgical resections, or cytology cell blocks. Billing for the molecular pathology panel uses 81459 for large genomic panels, and may be accompanied by appropriate professional component modifiers when separate interpretation or technical components apply. Turnaround times typically range from 7–21 calendar days depending on test complexity and laboratory workflow.

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	Use when billing separately for the interpretation/reporting by a qualified laboratory director or pathologist distinct from the technical component.
`TC`	Technical component	Use when billing only for the laboratory technical processes (sequencing, reagents, instrumentation) without the professional interpretation.
`90`	Reference (outside) laboratory	Use when the specimen is sent to an outside/reference laboratory that performs the test.
`91`	Data not provided in input.	Data not available in the input.
`QK`	Advanced diagnostic laboratory test (ADLT) – technical component	Use when the ADLT status requires specific modifier for the technical component billing.
`QX`	Advanced diagnostic laboratory test (ADLT) – CLIA-waived qualified laboratory personnel	Use when qualified personnel perform portions of the test per payer ADLT policies.
`QY`	Advanced diagnostic laboratory test (ADLT) – referring laboratory	Use when the test is performed by a referring laboratory under ADLT arrangements.
`AS`	Physician service: active clinical care	Use when the ordering physician is performing active management for the patient during the visit associated with testing.
`52`	Reduced services	Use when the test performed is a reduced service relative to the full panel (rare; document reduction).
`55`	Postoperative management only	Use in ancillary circumstances when only postoperative management is billed in conjunction with the procedure.

Taxonomy Code	Specialty	Notes
`207ZP0213X`	Pathology - Clinical Pathology/Laboratory Medicine	Laboratory directors and clinical pathologists who oversee molecular testing and interpretation.
`207Q00000X`	Family Medicine Physician	Ordering clinicians in outpatient settings who may request genomic profiling for screening/susceptibility contexts.
`207R00000X`	Internal Medicine Physician	Medical oncologists or internists ordering testing to guide cancer therapy; may bill evaluation and management services surrounding the test.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`Z13.79`	Encounter for other screening for genetic and chromosomal anomalies	Used when genomic profiling is performed as a screening/assessment for inherited or tumor-associated genetic anomalies.
`Z15.89`	Genetic susceptibility to other disease	Applicable when testing is ordered due to known or suspected genetic predisposition influencing cancer risk or management.
`Z79.899`	Other long term (current) drug therapy	May be used in documentation when patients are on chronic therapies that influence testing decisions or interpretation.
`I25.10`	Atherosclerotic heart disease of native coronary artery without angina pectoris	Present in the input list; may be a comorbidity documented on the chart but not directly related to tumor genomic testing.
`I21.9`	Acute myocardial infarction, unspecified	Present in the input list; represents an acute comorbidity that may affect timing or urgency of oncologic workup including genomic testing.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`81479`	Unlisted molecular pathology procedure	Used when a specific molecular test does not map to an existing CPT; may be used if aspects of testing fall outside the scope of `81459` or for novel assays requiring individual review.

Note: Only the related CPT codes provided in the input are listed above.

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 separately for the interpretation/reporting by a qualified laboratory director or pathologist distinct from the technical component.
`TC`	Technical component	Use when billing only for the laboratory technical processes (sequencing, reagents, instrumentation) without the professional interpretation.
`90`	Reference (outside) laboratory	Use when the specimen is sent to an outside/reference laboratory that performs the test.
`91`	Data not provided in input.	Data not available in the input.
`QK`	Advanced diagnostic laboratory test (ADLT) – technical component	Use when the ADLT status requires specific modifier for the technical component billing.
`QX`	Advanced diagnostic laboratory test (ADLT) – CLIA-waived qualified laboratory personnel	Use when qualified personnel perform portions of the test per payer ADLT policies.
`QY`	Advanced diagnostic laboratory test (ADLT) – referring laboratory	Use when the test is performed by a referring laboratory under ADLT arrangements.
`AS`	Physician service: active clinical care	Use when the ordering physician is performing active management for the patient during the visit associated with testing.
`52`	Reduced services	Use when the test performed is a reduced service relative to the full panel (rare; document reduction).
`55`	Postoperative management only	Use in ancillary circumstances when only postoperative management is billed in conjunction with the procedure.

Taxonomy Code	Specialty	Notes
`207ZP0213X`	Pathology - Clinical Pathology/Laboratory Medicine	Laboratory directors and clinical pathologists who oversee molecular testing and interpretation.
`207Q00000X`	Family Medicine Physician	Ordering clinicians in outpatient settings who may request genomic profiling for screening/susceptibility contexts.
`207R00000X`	Internal Medicine Physician	Medical oncologists or internists ordering testing to guide cancer therapy; may bill evaluation and management services surrounding the test.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`Z13.79`	Encounter for other screening for genetic and chromosomal anomalies	Used when genomic profiling is performed as a screening/assessment for inherited or tumor-associated genetic anomalies.
`Z15.89`	Genetic susceptibility to other disease	Applicable when testing is ordered due to known or suspected genetic predisposition influencing cancer risk or management.
`Z79.899`	Other long term (current) drug therapy	May be used in documentation when patients are on chronic therapies that influence testing decisions or interpretation.
`I25.10`	Atherosclerotic heart disease of native coronary artery without angina pectoris	Present in the input list; may be a comorbidity documented on the chart but not directly related to tumor genomic testing.
`I21.9`	Acute myocardial infarction, unspecified	Present in the input list; represents an acute comorbidity that may affect timing or urgency of oncologic workup including genomic testing.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`81479`	Unlisted molecular pathology procedure	Used when a specific molecular test does not map to an existing CPT; may be used if aspects of testing fall outside the scope of `81459` or for novel assays requiring individual review.

Note: Only the related CPT codes provided in the input are listed above.

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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Trek Health powers OpenPayer with a leading commercial payer intelligence platform, seamlessly converting fragmented payer data into actionable insights for provider organizations.