Background: The aim of this study was to determine whether circulating tumor cells (CTCs) have utility as a prognostic biomarker in stage II colorectal cancer (CRC), as well as a biomarker for the selection of patients for adjuvant chemotherapy. Methods: CTCs were detected in peripheral blood samples obtained from 73 stage II CRC patients, using a negative enrichment and immune-fluorescence in situ hybridization (imFISH) staining method. The follow-up time ranged from 3.5 to 35.9 months, and the clinic-pathologic characteristics and recurrence free survival (RFS) were collected and analyzed. Results: Seventy-three stage II CRC patients were included in this study. The positive rate of CTCs was 65.8% in all patients, 87.5% in recurrent patients and 59.6% in no recurrence patients. The mean RFS was 30.6 months for all patients, 28.7 months for CTC-positive patients and 34.0 months for CTC-negative patients (P=0.043). The mean RFS of CTC-positive and CTC-negative patients with adjuvant chemotherapy were not reached, and those without adjuvant chemotherapy were 27.7 and 33.4 months, respectively. Conclusions: The level of CTCs may be an effective prognostic factor to predict RFS in stage II CRC patients, and has potential in selecting stage II CRC patients for adjuvant chemotherapy.