Recently a possible cross talk about the relationship between p53 and beta-catenin has been suggested by the observation that colorectal cancers accumulating beta-catenin (as a result of APC mutations) also exhibit high frequency p53 mutations. Our aim was to evaluate the pattern of both the proteins and match these with the morphological changes in colorectal carcinogenesis. Immunohistochemical patterns of p53 and beta catenin were studied using the natural carcinogenetic model of malignant colorectal sporadic adenoma in 27 formalin-fixed paraffin-embedded polyps. We found a progressive increase of p53 and beta-catenin staining from normal, to dysplastic, and to cancerous epithelium. We noted, in dysplastic and cancerous epithelium, but not in normal tissue, the translocation of beta-catenin from the cytoplasm to the nucleus, and in dysplastic epithelium, a significant correlation between p53 over expression and beta-catenin patterns. Beta-catenin cytoplasmic accumulation seemed to drive p53 over expression already in the early stages of carcinogenesis, while nuclear beta-catenin translocation appeared to be related to a pattern of invasion of neoplastic cells.