Approximately half of all colorectal cancers show p53 (TP53) gene mutations, with higher frequencies observed in distal colon and rectal tumors and lower frequencies in proximal tumors and those with the microsatellite instability or methylator phenotypes. Alterations to-this gene appear to have little or no prognostic value for colorectal cancer patients treated by surgery alone, but are associated with worse survival for patients treated with chemotherapy. There is some evidence that different p53 mutations are associated with different clinical features including prognosis and response to therapy, although further large studies are required to confirm this. Several in vitro, animal and clinical studies have shown that normal p53 is required for the response of colorectal cancers to 5,fluorouracil,based chemotherapy. This should be confirmed by additional retrospective cohort studies and by the incorporation of P53 status in ongoing and future clinical trials. The evaluation of p53 overexpression, using a standardized immunohistochemical (IHC) procedure, could be a clinically useful marker for the identification of colorectal cancer patients likely to benefit from the standard chemotherapy regime currently used for this disease.