BACKGROUND & OBJECTIVE Transrectal ultrasonography (TRUS)-guided sextant biopsy technique was regarded as golden standard method for the diagnosis of prostate cancer. Recently, many reports show that the detection rate of prostate cancer by sextant biopsy is not high, and suggest to take more cores to improve the detection rate. But there is no ideal protocol now. This study was to explore an appropriate prostate biopsy protocol for the detection of prostate cancer. METHODS Clinical data of 325 consecutive men with suspected prostate cancer were analyzed. All patients underwent 12-core biopsy protocol (first biopsy) with additional 1 or 2 cores at each suspicious area detected by TRUS. The sensitivity of different combinations of biopsy cores was analyzed. RESULTS Of the 325 patients, 126 (38.8%) were positive for prostate cancer. The detection rate by 12-core protocol was significantly higher than maximal detection rate by 6-, 8-, and 10-core protocols (38.8% vs. 27.7%, 29.8%, and 35.4%, P<0.05). In the patients with prostate volume of <40 ml, there was no significant difference in detection rate of prostate cancer between 8-, 10-, and 12-core protocols. In the patients with prostate volume of 40-60 ml, the detection rate by 10-core protocol was significantly higher than that by 8-core protocol (36.2% vs. 26.9%, P=0.046). In the patients with prostate volume of >60 ml, the detection rate by 12-core protocol was significantly higher than that by 10-core protocol (37.9% vs. 25.8%, P=0.049). CONCLUSIONS Individual prostate biopsy protocol should be taken for the detection of prostate cancer. We recommend 8-core protocol for the patients with small prostate (<40 ml), 10-core protocol for the patients with the prostate of 40-60 ml, and 12-core protocol for the patients with the prostate of >60 ml, and add 1 or 2 cores or take focus biopsy protocol at suspicious areas detected by TRUS.