Background:This study was aimed to detect post-chemotherapeutic circulating tumour cells (CTCs) in stage III colon cancer patients and identify those who were at high risk of relapse.Methods:We used human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and carcinoembryonic antigen (CEA) as the biomarkers to detect CTCs in 90 stage III colon cancer patients undergoing curative resection followed by mFOLFOX chemotherapy.Results:Post-chemotherapeutic relapse occurred in 30 (33.3%) patients. By univariate analysis and multivariate proportional hazards regression analysis, perineural invasion (hazard ratio (HR): 2.752; 95% confidence interval (CI): 1.026-7.381), high post-chemotherapeutic serum CEA levels (HR: 2.895; 95% CI: 1.143-7.333) and persistent presence of post-chemotherapeutic CTCs (HR: 6.273; 95% CI: 2.442-16.117) were independent predictors of post-chemotherapeutic relapse. In addition, the persistent presence of post-chemotherapeutic CTCs strongly correlated with reduced disease-free survival and overall survival. Accuracy of detecting relapse in post-chemotherapeutic stage III colon cancer patients by analysing the persistent presence of post-chemotherapeutic CTCs was higher than that by post-chemotherapeutic CEA levels (odds ratio: 50.091 vs 5.211).Conclusion:The persistent presence of post-chemotherapeutic CTCs is a potential powerful surrogate marker for determining clinical outcome in stage III colon cancer patients receiving adjuvant mFOLFOX chemotherapy.British Journal of Cancer advance online publication, 19 February 2013; doi:10.1038/bjc.2012.595 www.bjcancer.com.