Overexpression of nuclear p53 and DNA ploidy were analyzed in a series of 65 colorectal adenocarcinomas and correlated with standard clinical and pathological variables (Dukes stage, tumor site, histological grade and type, and nature of the tumor margins). Immunohistochemical tests were done with the DO-7 monoclonal antibody, using formalin-fixed tissue samples and an antigen retrieval solution. Levels of p53 expression were evaluated using a semiquantitative grading system (CAS 200, BD). Nuclear staining of more than 15% of neoplastic cells was observed in 35 samples (53.8%), which were classified as p53-positive. DNA content was measured by flow cytometry in samples of fresh tissue. Tumor site had a significant direct relationship with DNA ploidy (p < 0.01) and p53 expression (p < 0.001). Proximal tumors were more frequently diploid than were distal tumors (78.6% vs 32%). Moreover, distal neoplasms showed more p53 expression than proximal tumors (64.6% vs 14.3%). However, there was no correlation between the other clinical or pathological variables and the pathological parameter p53 expression and DNA ploidy. Our data support the hypothesis that mechanisms of colorectal carcinogenesis may differ in proximal and distal neoplasms.