Most investigators agree that the most common antecedent of cancer in a breast is cancer in the opposite site. Thus, the present study focused on investigating the incidence of p53 gene abnormality in bilateral breast cancer and its correlation with proliferative activity and nuclear cytomorphology to demonstrate its significance in biological behavior and predicting the relatively small percentage of second tumors in the contralateral breast. Paraffin embedded tissue specimens obtained from 18 patients with bilateral primary breast cancer were studied. Ki-67 expression, a marker of tumor cell proliferation, was scored and p53 gene abnormalities were detected by avidin-biotin-peroxidase immunostaining. The mean nuclear volume of the tumor cells was assessed by a stereologic method. p53 gene abnormalities were detected in eight cases (44.4%). Seven cases (38.8%) exhibited strong Ki-67 immunopositivity, 10 cases (55.5%) exhibited weak Ki-67 immunopositivity and one case (5.5%) exhibited negative immunostaining. The mean nuclear volume was found to be 315.9 +/- 94.3 microm3 overall. The correlation between p53 mutations and the Ki-67 expression was statistically significant (P = 0.017, chi2-test), whereas the assessment of the mean nuclear volume also indicated significant correlation with p53 (P = 0.024, independent-samples t-test). However, we did not find any correlation between p53 mutation and either hormone receptor status or histological grade (P = 0.52, Fisher's test and P = 0.72, chi2-test, respectively). We have concluded that p53 gene abnormalities are detected in almost half of the bilateral breast cancers and are associated with high proliferative activity and mean nuclear volume. Although so far the number of patients is too small and the follow-up too short to determine the definitive prognostic value of p53 mutation, our preliminary results have indicated that it might be an indicator of a worse prognosis in bilateral breast cancer and a predictor of cancer in the contralateral breast.