The aim of this study is to elucidate the diagnostic efficacy between transperineal and transrectal 12-core prostate biopsy for prostate cancer. We prospectively randomized 200 consecutive men into two groups to undergo systematic prostate biopsy. Overall positivity for cancer was similar (47% by transperineal and 53% by transrectal; P=0.480). However, in case with 'gray zone' PSA (from 4.1 to 10.0 ng/ml), significantly more cores were positive when approach was transperineal, especially among transition zone cores. Therefore, urologist preferences are sufficient for choosing an approach, except for a possible small advantage of transperineal biopsy when PSA is in gray zone.