Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)OBJECTIVE: To describe the behavior of alpha-methylacyl coenzyme A racemase (AMACR) in focal atrophy including all subtypes. Focal prostatic atrophy is the benign lesion that most frequently mimicks adenocarcinoma particularly the partial variant. STUDY DESIGN: We analyzed the immunohistochemical expression of AMACR in normal glands and acini of adenocarcinoma, partial atrophy and all variants of complete atrophy of a total of 1,198 acini on needle prostatic biopsies. RESULTS: Partial atrophy showed negative and weak expression of AMACR in 143/190 (75.3%), and 47/190 (24.7%) acini, respectively. The secretory (luminal) compartment in all variants of complete atrophy showed aberrant immunohistochemical expression: AMACR negative, prostate-specific antigen negative and 34 beta E12 positive, suggesting an intermediate phenotype for these cells. CONCLUSION: No strong positivity was seen in partial atrophy; however, the absence of basal cells in 23.2% acini of partial atrophy and the weak positivity seen in 24.7% acini that overlaps with 22.5% acini with weak expression in adenocarcinoma may be a pitfall for the correct interpretation in the differential diagnosis of cancer. Recognizing the hematoxylin-eosin features of partial atrophy is still the most critical aspect in preventing a misdiagnosis of adenocarcinoma. (Anal Quant Cytol Histol 2009;31:424-431)316424431Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)