Purpose: Previous studies have indicated that 6-core transrectal prostate biopsy misses a considerable number of cancers. We performed an extensive biopsy protocol of 12-core sampling using both transperineal and transrectal approaches to determine the impact on the cancer detection rate. Materials and methods: We prospectively evaluated 402 men who underwent 6-core transperineal and 6-core transrectal biopsies simultaneously due to abnormal digital rectal examination (DRE) and/or elevated prostate-specic antigen (PSA) levels of 4.0 ng/mL or greater. Using the transperineal approach we obtained four cores from the bilateral peripheral zone targeting the lateral and parasagittal areas and two cores from the bilateral transition zone. The following transrectal biopsy was performed traditionally. We compared cancer detection rate between the extended 12-core procedure and conventional 6-core transperineal and transrectal groups in terms of total PSA and DRE ndings. Results: Using the extensive combined method, prostate cancer was detected in 195 cases (48.5%) and the detection rate signicantly increased 7.2% and 8.5% compared to the transperineal and transrectal groups, respectively. According to PSA levels and DRE ndings, the cancer detection rate by the combined method was signicantly improved in patients with PSA levels of 4-10 ng/mL and negative DRE: 10.3% and 11.6% compared to the transperineal and transrectal groups, respectively. Conclusions: The extensive 12-core method signicantly improved the overall cancer detection rate and was especially efcient for men with PSA levels of 4-10 ng/mL accompanied by a negative DRE nding.