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Partial atrophy is the most common benign mimicker of prostate cancer on needle biopsy. Of 3916 prostate needle core biopsy cases received in our consultation service over a period of 3 months (March 1, 2007 to May 31, 2007), 170 cases (4.3%) with partial atrophy were diagnosed as atypical glands by outside pathologists and prospectively identified. We supplemented our material with 108 cases of partial atrophy sent to our consultation service in 2006 from a single institution, which frequently uses a triple cocktail stain [p63, high molecular weight cytokeratin (HMWCK), α-methyl acyl-Coa racemase (AMACR)]. The morphologic features of the 278 cases and immunohistochemistry of 236 cases (198 with prostate cocktail and 38 with only basal cell makers) were analyzed. Forty-eight of 278 (17.3%) partial atrophy cases were mixed with postatrophic hyperplasia. Enlarged nuclei were visible in 43/278 (15.5%) cases, with prominent nucleoli seen in 58/278 (20.9%) cases (30 cases associated with nuclear enlargement). Of 198 cases with a prostatic cocktail stain, 48 (24.2%) had a cancer pattern for both basal cells and AMACR (p63−, HMWCK−, and AMACR+), 14 (7.1%) had a cancer pattern for basal cells (p63−, HMWCK−, and AMACR−), 89 (44.9%) had a cancer pattern for AMACR (p63+, HMWCK+, and AMACR+), and 47 (23.7%) had a totally benign pattern (p63+, HMWCK+, and AMACR−). Of the 198 cases using the cocktail stain, 136 (68.7%) had positive basal cell staining. The percentage of basal cells labeled with the combination of p63/HMWCK was: <5% in 42 (21.2%) cases, 5% to 75% in 58 (29.3%) cases, and >75% in 36 (18.2%) cases. An additional 38 cases immunostained only for p63 and/or HMWCK was negative in 2 (5.2%) cases, <5% (13.1%) in 5 cases, 5% to 75% in 19 (50%) cases, and >75% in 12 (31.6%) cases. In conclusion, partial atrophy is a benign mimicker of adenocarcinoma both as a result of its routine morphologic features and its immunohistochemical profile. Recognition of the classic morphology of partial atrophy on routine hematoxylin and eosin-stained sections is critical to avoid misdiagnosing partial atrophy as adenocarcinoma.