Several investigators have reported the correlation of p53 and bcl-2 immunoreactivity with post operative prostate specific antigen (PSA) recurrence. Focal and or clustered expression is typical for these biomarkers. The purpose of this study was to compare the effectiveness of tissue microarrays to detect p53 and bcl-2 overexpression and their prognostic significance. Tissue microarrays (TMA) of 99 patients with mean follow-up of 61 months contained 760 samples from 241 carcinomas, 431 benign glands, and 88 foci of prostatic intraepithelial neoplasia (PIN). Overexpression of p53 was seen in 43.3% of 97 patients, whereas bcl-2 overexpression was noted in 23.7% of 97 patients using TMA technology, compared to 66.0% and 26.9%, respectively in the corresponding radical prostatectomy samples. The tissue microarray technology is a powerful tool to study the multifocal and heterogeneous nature of prostate cancer. However, the prognostic value of p53 and bcl-2 could not be confirmed using this technology in contrast to radical prostatectomy sections. The TMA technique is probably more informative and reliable in evaluating the prognostic value of homogeneously expressed biomarkers.