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Dihydropyrimidine dehydrogenase (DPD) is an enzyme that catabolizes 5-fluorouracil (5-FU), which is widely used for chemotherapy in patients with advanced colorectal cancer (CRC). However, the clinical importance of tumor dihydropyrimidine dehydrogenase (DPD) expression in patients with CRC treated with 5-FU remains unclear.We investigated DPD activities in normal mucosa (N) and tumors (T) by enzyme-linked immunosorbent assay (ELISA) in 64 surgically resected patients with Dukes' C CRC who were treated orally with postoperative adjuvant FU-based chemotherapy. We also immunohistochemically investigated DPD expression in these specimens. The clinicopathological importance of DPD activity and expression was evaluated in the patients.Positive DPD expression was detected in 28 tumors (43.8%) and tumor DPD activity significantly correlated with tumor DPD immunoreactivity (p=0.0121). Further, tumor DPD activity and immunoreactivity also correlated with lymph node metastatic status (p=0.0409). The disease-free survival rate of patients with positive-tumor DPD expression was significantly worse than that of patients with negative-tumor DPD expression (39.3% vs. 72.2%, p=0.0127). However, DPD activity in tumors or normal mucosa did not correlate with patient prognosis. Tumor DPD expression appeared to be an important poor prognostic factor in patients with Dukes' C CRC by multivariate analysis (p=0.013).Immunohistochemical DPD expression in tumors is a useful prognostic parameter in patients with Dukes' C CRC treated with postoperative adjuvant FU-based chemotherapy.