Rectal adenocarcinomas is usually associated to a poorer outcome than colon cancers. In this study we analyzed the impact on overall survival of p53 and Bcl-2, evaluated by immunohistochemical techniques, in 126 advanced rectal cancer patients submitted to 5 fluorouracil based adjuvant therapy. Shorter overall survival was observed in patients bearing p53 positive and Bcl-2 negative tumors, although in multivariate analysis only p53 emerged as independent predictor of a worse outcome. These results seem to indicate that, in stage III-IV rectal cancer, p53 alterations may identify high risk patients to be enrolled in more aggressive and/or innovative adjuvant/neoadjuvant treatments.