Standard sextant prostate biopsy may underestimate cancer in men in whom clinical finding and transrectal ultrasound are negative and prostate-specific antigen (PSA) value suspicious for localized prostate cancer (4-10 ng/ml). We describe our experience with a 14 systematic multisite biopsy scheme to detect carcinoma of the prostate (stage T1c). Between January 1999 and February 2000, a total of 177 consecutive patients (mean age 64.1 +/- 7.7 years) underwent systematic transrectal ultrasound (TRUS) guided biopsy for normal digital rectal examination, normal TRUS and abnormal prostate specific antigen 4 ng/ml or greater (4-13 ng/ml). Fourteen core/patient were obtained not depending on prostate size. Biopsies were obtained from conventional sextant biopsies (6 core) and 3 alternate sites which included: the right and left extreme lateral peripheral zone between anterior tissue and posterior gland base (2 core); the right and left transition zone, immediately adjacent to the urethra anterior and posterior (4 core) and the right and left central gland in the mid zone typical of benign prostatic hyperplasia (BPH) (2 core). All specimens were separated for specific location identification. Adenocarcinoma was identified in 61 patients (34.46%). Traditional sextant biopsies showed 23 patients (37.7%) with positive core to detect cancer, while a sextant regimen incorporating lateral peripheral zone biopsies and transitional zone detected 19 cancer (31.1%). The combination of lateral peripheral and transitional zone alone detected cancer in 19 patients. No cancer was detected in central gland. The lateral peripheral zone was the most frequently positive site biopsy with 11 patients (57.9%) followed by the transitional zone with 8 patients (42.1%) in the group of the alternate biopsies sites. Complications of extensive biopsy included hematuria, hematospermia and limited rectal blending in 95% of patients; 1 case of fever (> 38.5 degrees C) for 3 days. Biopsies of the alternate sites are easy, feasible and reproducible. This strategy enhance prostate cancer detection of a 30% compared to conventional sextant biopsies alone. In conclusion, the 6 systematic biopsy of the peripheral zone are inadequate and a minimum of 12 with extensive core in peripheral and transitional zone should routinely be performed to detect a more significant number of men with prostate cancer at stage T1c.