[en] The pathologist's responsibility is to accurately grade and stage prostate cancer through evaluation of tissue specimens. The Gleason system is the most widely used and independently validated grading system in the United States and is gradually replacing other grading systems world-wide. This system relies only on architectural characteristics of the tumor from low magnification microscopy without regard to nuclear grade. In nearly all studies evaluating old and new prognostic parameters, the Gleason grade has been shown consistently to be the most powerful independent prognostic factor. Attempts to distinguish between clinically significant and clinically insignificant cancer prior to any therapy have utilized a combination of clinical and pathologic parameters such as: DRE and TRUS findings, serum PSA, and Gleason grade, number of biopsy cores involved, and length of tumor in each of the involved cores. Other markers that are being studies to enhance prediction of final pathologic stage include microvessel density (angiogenesis), DNA ploidy, and immunohistochemistry for various markers such as p53 protein product. Accurate pathologic staging of the radical prostatectomy specimen with or without pelvic lymph node dissection is the gold standard with which to compare all other less invasive means of evaluation. The most complete information is derived from a totally embedded and sectioned radical prostatectomy specimen, either by standard or whole-mount sections. The pathologic staging consists of evaluation for the presence or absence of extraprostatic extension, seminal vesicle involvement, and lymph node metastases. Surgical margin status, although a potentially important piece of prognostic information, is not a part of any pTNM category. Following treatment of prostate cancer by definitive irradiation therapy, assessment of local control of the tumor is based upon clinical and radiographic criteria along with the results of follow-up biopsies. There are differences of opinion regarding the meaning of the post-irradiation biopsy, but no controversy regarding the fact that many months may pass after therapy before biopsy findings have any clinical relevance. Another practical difficulty is that many pathologists are not familiar with the interpretation of the post-irradiation biopsy, giving rise to false positive diagnoses when irradiation-induced atypia in residual benign glands is mistaken for residual carcinoma