Background: Stratification of localized prostate cancer based on disease aggressiveness remains challenging, resulting in overtreatment of low-risk patients and under treatment of high-risk patients. A biopsy-based, cell cycle progression (CCP) gene expression assay can aid physicians in predicting prostate cancer aggressiveness, leading to more appropriate patient management. This study quantifies the economic impact of the CCP assay on a US commercial health plan. Methods: A fact-based economic model was developed for a hypothetical cohort of prostate cancer patients with localized disease. Patients were followed in the model for 10 years with management and progression assumptions based on published clinical data and interviews with board-certified physicians. Total cost of care was calculated for a reference scenario (current clinical practice) and a test scenario where patient management was altered based on CCP test results. Cost inputs were set for each unit of care that a patient might undergo (diagnostic/surgical/radiotherapy procedures and pharmacological therapy); costs were assigned based on published costs of care. Total cost of care was compared between the two scenarios to determine overall system economic impact. Results: The CCP test reduced costs by $2,850/patient tested over 10 years after accounting for test cost. For a health plan with 10 million members, this would translate to over $16 million in savings with two-thirds of those savings achieved in the first year after testing. The majority of savings came from increased use of active surveillance in AUA low- and intermediate-risk patients. No single model input, when changed within a range of values, caused the model to show that the test was no longer cost saving. Costs of the test scenario were never greater than the reference scenario, resulting in cost savings over the 10 years modeled. Conclusions: Use of the CCP test in a US commercial health plan has the potential to result in cost savings to payers. Savings are due to increased use of active surveillance in low- and intermediate-risk patients with less aggressive disease, but also from reduced progression rates in high-risk patients with more aggressive disease who transition to multi−modality therapy.