Expression of c-erbB-2 and p53 protein was analysed retrospectively by immunohistochemistry in formalin-fixed tissue samples from 293 patients with colorectal adenocarcinoma. There was a significant positive relationship between c-erbB-2 and p53 expression (P < 0.0001). Co-overexpression of c-erbB-2 and p53 tended to be increased in tumours with infiltrative growth (P = 0.08) and higher S-phase fraction (P = 0.085). In combined survival analysis, patients with tumours in both c-erbB-2 positivity and p53 negativity had a more favourable outcome (P = 0.03). Multivariate analysis revealed that p53 overexpression was significantly associated with poor prognosis independent of c-erbB-2 expression, DNA-ploidy, S-phase fraction, growth pattern and Dukes stage (P = 0.002). We conclude that there is an inter-reaction between the two oncoproteins in the tumour development and that the overexpression of p53 proteins may be a powerful prognostic predictor in colorectal adenocarcinoma.