The aim of this study was to evaluate the prognostic significance of tumor dihydropyrimidine dehydroganase (DPD) in curatively resected colorectal cancer patients who received or did not receive oral 5-FU based-adjuvant chemotherapy. Among 182 patients with stage II-III colorectal cancers, 89 patients (adjuvant chemotherapy group) received oral 5-FU based-adjuvant chemotherapy, and 93 patients (surgery alone group) did not receive 5-FU. DPD expressions in the tumors and in the normal colonic mucosa were measured by enzyme-linked immunosorbent assays. The mean DPD expression of the tumors was significantly lower than that of the normal mucosa (54.4 +/- 40.4 versus 72.3 +/- 23.3 Unit/mg protein, P < 0.01). For survival analyses, we designated the cut-off value of tumor DPD as its median value (46.3). In the adjuvant chemotherapy group, high tumor DPD levels were associated with poor survival (HR, 5.24; P = 0.03). In the surgery alone group, high tumor DPD levels were associated with better survival (HR, 0.32; P = 0.02). In conclusion, tumor DPD level is an efficacious marker in oral 5-FU based-adjuvant chemotherapy for colorectal cancer; however, low tumor DPD predicts reduced survival in patients treated with curative surgery alone.