To investigate the expression of CD44 in colorectal cancer and examine its association with clinicopathological features, bcl-2, p53 and long-term outcome, paraffin-embedded tumour specimens from 61 patients with Dukes stage B (AJCC/UICC stage I) and 39 patients with Dukes stage C (AJCC/UICC stage III) colorectal adenocarcinoma were assessed by immunohistochemistry. The expression of CD44, bcl-2 and p53 were correlated with 5-year follow-up. Low CD44 expression was present in 30%, moderate in 30% and extensive in 40% of cases. It was not related to patient sex and age but was related to tumour differentiation, stage and tumour site. No association was demonstrated between CD44 and bcl-2. However, there was significant evidence of an association between CD44 and p53 in 66 cases in which p53 was previously assessed. There was a trend towards increased survival in patients whose tumours expressed lower levels of CD44 protein. When entered into multivariate analysis model, which also included bcl-2 and p53, CD44 staining emerged as an indicator of poor prognosis in colorectal cancer patients.