The risk factors for colon cancer recurrence following a curative intent surgery include the tumor location and size, the presence of adhesions, perforation, bowel obstruction, depth of invasion, histological grade, percentage of S phase content and cell kinetic profile. The DNA content of tumor cells has recently been suggested as an additional prognostic factor. In this study we assessed the tumor ploidy as a prognostic factor for recurrence and survival in colon cancer patients. The DNA content of colon cancers in 20 Dukes' B2 patients followed up at our center, who relapsed either locally or systemically, following surgical treatment was measured by image analysis. The data were pair-matched for age, sex, tumor site and grade, and the period of follow-up with 20 Dukes' B2 patients who had no evidence of disease. Aneuploidy occurred in 16 (80%) patients with recurrence, whereas only in 8 (40%) in the control group. Nonaneuploid DNA content was found in 12 (60%) patients of the control group, but in only 4 (20%) patients with a relapse. Aneuploidy was associated with a significantly higher tumor recurrence rate (p = 0.024) and shorter overall survival (p < 0.002). Our data point to a possible indication of a systemic adjuvant chemotherapy in Dukes' B2 colon cancer patients who have aneuploid tumors on image analysis. This should be further investigated in a prospective controlled randomized study.