Context: The number and location of biopsy cores and the interpretation of prostate biopsy in different clinical settings remain the subjects of continuing debate. Objective: Our aim was to review the current evidence regarding the performance and interpretation of initial, repeat, and saturation prostatic biopsy. Evidence acquisition: A comprehensive Medline search was performed using the Medical Subject Heading search terms prostate biopsy, prostate cancer, detection, transrectal ultrasound (TRUS), nomogram, and diagnosis. Results were restricted to the English language, with preference given to those published within the last 3 yr. Evidence synthesis: At initial biopsy, a minimum of 10 but not > 18 systematic cores are recommended, with 14-18 cores in glands >= 50 cm(3). Biopsies should be directed laterally, and transition zone (TZ) cores are not recommended in the initial biopsy setting. Further biopsy sets, either as an extended repeat or as a saturation biopsy(>= 20 cores) including the TZ, are warranted in young and fit men with a persistent suspicion of prostate cancer. An immediate repeat biopsy is not indicated for prior high-grade prostatic intraepithelial neoplasia diagnosis given an adequate extended initial biopsy. Conversely, biopsies with atypical glands that are suspicious but not diagnostic of cancer should be repeated within 3-6 mo. Overall recommendations for further biopsy sets (a third set or more) cannot be made. Transrectal ultrasound-guided systematic biopsies represent the standard-of-care method of prostate sampling. However, transperineal biopsies are an up-to-standard alternative. Conclusions: The optimal prostatic biopsy regimen should be based on the individualized clinical setting of the patient and should follow the minimum standard requirements reported in this paper. (C) 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.