In order to investigate the genomic instability associated with prostate cancer, 36 microsatellite marker loci on chromosomes 1p, 3p, 5q, 8p, 8q, 9p, 11q and 13q were analyzed using microdissected samples from prostate cancer and adjoining microscopically normal tissues from the same slide. DNA was extracted from the normal and tumor cells of 40 microdissected prostate-cancer samples, amplified by PCR, and analyzed for microsatellite instability (MSI) using 36 different polymorphic DNA markers. In the present study, we have utilized a highly refined technique of PCR product separation on a sequencing gel, developed in our laboratory, which clearly shows high-quality results for the microsatellite instability in prostate cancer. The results of this study suggest that 45% (18 out of 40) showed genomic instability at a minimum of 1 locus; 4 cases each showed MSI at one and 2 loci, 4 cases had MSI at 3 loci, 3 cases showed MSI at 5 loci, while one case each showed MSI at 7, 8 and 15 loci. There was no significant correlation between the MSI and stage or grade of the tumors. This extensive study on genomic instability in prostate cancer found the occurrence of MSI to be very high, which suggests a role of MSI in the pathophysiology of prostate cancer.