ABSTRACT Purpose: Detection rate for anterior prostate cancer (PCa) in men who underwent initial and repeat biopsy has been prospectively evaluated. Materials and Methods: From January 2013 to March 2014, 400 patients all of Caucasian origin (median age 63.5 years) underwent initial (285 cases) and repeat (115 cases) prostate biopsy; all the men had negative digital rectal examination and the indications to biopsy were: PSA values > 10 ng/mL, PSA between 4.1-10 or 2.6-4 ng/mL with free/total PSA≤25% and ≤20%, respectively. A median of 22 (initial biopsy) and 31 cores (repeat biopsy) were transperineally performed including 4 cores of the anterior zone (AZ) and 4 cores of the AZ plus 2 cores of the transition zone (TZ), respectively. Results: Median PSA was 7.9 ng/mL; overall, a PCa was found in 180 (45%) patients: in 135 (47.4%) and 45 (36%) of the men who underwent initial and repeat biopsy, respectively. An exclusive PCa of the anterior zone was found in the 8.9 (initial biopsy) vs 13.3% (repeat biopsy) of the men: a single microfocus of cancer was found in the 61.2% of the cases; moreover, in 7 out 18 AZ PCa the biopsy histology was predictive of significant cancer in 2 (28.5%) and 5 (71.5%) men who underwent initial and repeat biopsy, respectively. Conclusions: However AZ biopsies increased detection rate for PCa (10% of the cases), the majority of AZ PCa with histological findings predictive of clinically significant cancer were found at repeat biopsy (about 70% of the cases).