We aimed to clarify the clinical significance of circulating tumor cells (CTCs) in the tumor drainage vein blood of colorectal cancer(CRC) patients with Dukes' stage B and C. This study included 111 patients with Dukes' stage B and 86 patients with Dukes' stage C. We selected multiple genetic markers, including the cancer-associated marker (CEA), epithelial markers(CK19 and CK20), and cancer stem-like cell marker(CD133), and the mRNA levels of these genes were detected by quantitative real-time reverse transcription-polymerase chain reaction assays. In Kaplan-Meier survival curve analysis, overall survival(OS) and disease-free survival(DFS) of Dukes' stage B and C patients who were positive for CEA, CK19, CK20, and/or CD133 (CEA/CK/CD133) were significantly worse than that in patients who were negative for these markers. By Cox progression analysis, it was demonstrated that CEA/CK/CD133 mRNA in tumor drainage vein blood was an independent prognostic factor for OS and DFS in these patients. These results suggest that CEA/CK/CD133 mRNA detection in tumor drainage vein blood is a useful tool for the determination of high-risk CRC patients with Dukes' stage B and C who are in need of postoperative adjuvant therapy.