To evaluate both the clinicopathological and prognostic significance of p53 protein, the expression of p53 protein was immunohistochemically examined by use of CM1, PAb1801, DO7, and DO1 antibodies on paraffin-embedded colorectal adenocarcinomas from 293 patients. Overexpression of the p53 protein was present in 49% of the samples studied with CM1, 18% with PAb1801, 30% with DO7, and 44% with DO7. The p53 overexpression, as detected by any of the antibodies, tended to associate with distal colorectal, non-mucinous, DNA nondiploid, and higher proliferatively active tumors (P < 0.05) but was irrespective of the patient's gender, age, tumor growth pattern, or Dukes' stage (P > or = 0.05). The p53 protein that was detected by CM1 in either the nucleus (P = 0.007) or the cytoplasm (P = 0.0005) was an independent prognostic indicator. DO1 staining correlated with poor prognosis in the patients with Dukes' B tumor (P = 0.02). However, neither PAb1801 nor DO7 staining could predict prognosis (P > 0.05). p53-positive staining by any of the antibodies predicted significantly poor prognosis compared with p53-negative reactivity (P = 0.007). These results suggest that there was essentially no difference in the significance of p53 overexpression as detected by any of the four antibodies with regard to clinicopathological variables. However, CM1 was the best antibody for predicting prognosis in this series of colorectal cancer patients.