Aims: To assess the value of thymidylate synthase (TS) expression as a predictive factor in the efficacy of adjuvant chemotherapy in colorectal cancer, as well as its independent prognostic value for survival. Methods: We studied 114 high risk colorectal carcinoma patients (high risk stage 11 and stage 111), distributed in two treatment groups: surgery alone (61 patients) or surgery followed by 5-FU-based chemotherapy (53 patients). TS protein expression in the tumour tissue was assessed by immunohistochemistry. Results: In the surgery atone subgroup, overall survival (OS) at 5 years were 77.5% for the patients with low TS expression, against 57.7% for the patients with high TS expression (p = 0.006). Among patients with low TS, there was no difference in OS as a result of whether adjuvant chemotherapy was carried out or not (65.8 vs 77.5%, p = 0.29). Among the patients with high TS, there was a significant gain in OS in favor of chemotherapy (87.8 vs 57.7%, p = 0.04). Analyzing the complete sample, TS expression was not shown as an independent prognostic factor for survival in the multivariate analysis. Conclusions: The immunohistochemical TS expression may be used for selecting patients for better adjuvant chemotherapy protocols. In this sample, TS expression was not an independent prognostic factor for survival. (c) 2005 Elsevier Ltd. All rights reserved.