The prognostic significance of p53 and bcl-2 expression in prostate carcinoma is currently under investigation. The aim of the present study was to analyze their expression in diagnostic biopsies and in prostatectomies performed after neo-adjuvant hormonal therapy to investigate their role in hormone resistance. One hundred and six patients with advanced prostate carcinoma were treated for 3 months with LHRH analogues before radical surgery. The expression of p53 and bcl-2 was analyzed by immunohistochemistry in all cases of prostatectomy and in available biopsies obtained before treatment, and was correlated with clinicopathologic parameters and follow-up. A significant increase in p53 expression was found following hormonal therapy, whereas no changes were observed in the expression of bcl-2. The increase in p53 did not correlate with the presence of therapy-induced morphological changes in prostate cancers, but it did correlate significantly with histologic grade and pathologic stage, biochemical progression of the disease, and short overall survival. At multivariate analysis, only grade and stage proved to be independent predictors of shorter survival. There were no correlations between bcl-2 and clinicopathologic variables whether in biopsies or in prostatectomies. The unfavorable clinical course associated with p53-positive carcinomas suggests that neo-adjuvant hormonal therapy may cause the selection of minor p53 mutated clones, rather than the induction of wild-type p53. In any case, the enhanced expression of p53 could label hormone-resistant cancers for further adjuvant therapy.