A 21-samples saturation biopsy procedure (SBP) was developed in order to improve prostate cancer detection rate. Out of 650 patients who underwent this protocol, 150 had a clinically localized prostate cancer and underwent a radical prostatectomy. The number of cores positive for tumor was assessed in the SBP, and also in the sextant component of the SBP (SC) and in the non-sextant component of the SBP (NSC). Numbers of cores positive for tumor on SBP, SC, and NSC were significantly higher in pT3 group versus pT2 (P < 0.001 each) and in positive surgical margins (PSM) group versus no PSM (P < 0.001 each). When comparing area under the curve obtained from SBP with those obtained from NSC and SC, the SBP showed higher accuracy than the NSC and the SC for the prediction of pT3 and PSM. On multivariate analyses, SC and NSC were independent predictors of pT3 and PSM on radical prostatectomy.