BACKGROUND.Focal targeted therapy has been proposed as a potential treatment for localized prostate cancer in an attempt to reduce morbidity. However, these modalities rely heavily on accurate tumor localization to achieve total tumor ablation. In the current study, we sought to examine the ability of contemporary extended pattern prostate biopsy to predict the location of tumors.METHODS.A total of 281 men with prostate cancer detected via a standardized extended pattern biopsy template with at least 12 cores and who subsequently underwent radical prostatectomy were evaluated. Tumor location on biopsy, stratified by laterality and by site (apex vs mid‐base prostate), was compared with corresponding locations on the prostatectomy specimen. Generalized estimating equation models were developed to assess the effects of clinical variables on pathologic agreement between biopsy and prostatectomy specimens.RESULTS.Of the 281 prostate biopsies, the positive predictive value (PPV) of right and left needle biopsy was high at 97.3% and 96.7%, respectively. However, the negative predictive value (NPV) was low at 24.7% and 31.3%, respectively. When more specific locations were considered, the NPV improved at the apex. However, this came at a cost to the PPV. Tumor focality on prostatectomy specimen was the only clinical feature found to be significantly and consistently related to pathologic agreement.CONCLUSIONS.Contemporary extended pattern prostate biopsy, although able to diagnose cancers, fails to provide reliable localization of tumors to specific areas of the prostate. Focal therapy, which relies heavily on localization, should only be performed with this caveat in mind. Cancer 2008. © 2008 American Cancer Society.