The aim of this study was to clarify whether increased 5-fluorouracil (5-FU) uptake by tumor tissue following preoperative UFT administration is a prognostic factor after surgery in colorectal cancer patients. We examined the concentrations of 5-FU in tumor or normal tissue of 96 colorectal cancer patients who received UFT (400 mg/day) orally for 7 days prior to surgery. Patients were divided into two groups with high or low 5-FU concentrations in tumor tissue (defined as higher or lower than the cut-off value, respectively). The cut-off value of 5-FU was established based on the upper limit of the 95% confidence interval of the median of the concentration found in normal tissue (0.106 microg/g). Of the 96 patients, 62 (64.6%) were in the low-5-FU group and 34 (35.4%) in the high-5-FU group. The latter had a more favorable clinical outcome (p=0.0465). Cox regression analysis revealed that two independent variables, stage and 5-FU status in tumor tissue, were significant for prediction of survival. These findings suggest that increased uptake of 5-FU by tumor tissue following preoperative oral administration of UFT is an independent prognostic factor in colorectal cancer patients. This variable needs to be considered in the design of future therapeutic trials.