As individual risk assessment mainly depends on the correct prediction of the tumor's biological behavior, primary diagnosis plays a key role in the clinical management of prostate cancer patients. Prostate core needle biopsy, as a primary diagnostic tool, should not only confirm clinical suspicion but also supply the urologist with information which is necessary for risk-adapted therapy. The experience and competence of both the urologist and the pathologist are crucial for the quality of prostate core needle biopsy diagnosis. Optimized handling and submission of prostate core needle biopsy specimens by the urologist to the pathologist are of outstanding importance for improving the number of cancer cases detected. Increasing availability of molecular markers leads to the necessity of developing new tissue sampling procedures which allow prostate core needle biopsy specimens to be simultaneously studied histologically and by molecular approaches.