OBJECTIVES: Multi-gene assays and microarray technologies are being used increasingly for risk stratification of stage II colon cancer patients to predict disease relapse and guide adjuvant therapy decisions. Our objective was to evaluate the outcomes and cost-effectiveness of using ColoPrint (Agendia Inc., Irvine, CA) as compared with Oncotype DX Colon Cancer Assay (Genomic Health Inc., Redwood City, CA) in the treatment of stage II colon cancer patients. METHODS: As part of a larger study to develop a Markov model, we conducted a review of the literature from January 2005 to December 2016 to assess data on risk classification; recurrence rates, transition probabilities, utilities and costs used for GEP assays in patients with stage II colon cancer. We investigated outcomes in three stages - no recurrence, recurrence, and death. For costs, we considered gene test costs; the costs of adjuvant chemotherapy, costs associated with adverse events and treatment, the cost of treating recurrence, and end-of-life care costs. RESULTS: A retrospective data analysis of 6,064 patients for both multi-gene assays in stage II or III colon cancer was conducted. We found that the recurrence score (RS) and microsatellite (MSI) status are the most reliable factors for prognosis of stage II colon cancer patients. For 5,307 patients using Oncotype DX, we found RS of 780 patients (14.69%) were in the low risk group, 990 patients (18.65%) in the intermediate risk group and 950 patients (17.90%) in the high-risk group. For 757 patients using ColoPrint, we found that the MSI status of 485 patients (64.06%) was in the low risk group and 272 patients were (35.93%) in the high-risk group. CONCLUSIONS: Multi-gene assays can predict the development of distant metastasis of patients with stage II colon cancer and may improve prognostic accuracy for safe therapeutic management of patients in treatment decisions about chemotherapy.