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α-Methyl acyl coenzyme A racemase (AMACR) and cyclooxygenase-2 (COX-2) appear to contribute to the accurate diagnosis of prostatic adenocarcinoma (PAC), but neither is absolutely specific for PAC diagnosis and their results in previous studies have been controversial. The objectives of this study were to scrutinize the utility of AMACR versus COX-2 in PAC diagnosis, to identify which of them is more sensitive and specific for PAC, and to correlate their expressions in relation to Gleason score and tumor stage.Fifty-eight archival specimens for benign prostatic hyperplasia (BPH) and PAC were subjected to immunostaining using a rabbit monoclonal antibody for AMACR and a monoclonal rabbit anti-human antibody for COX-2. Any degree of cytoplasmic positivity for AMACR and either nuclear or cytoplasmic positivity for COX-2 were considered positive. The percentage of positive cells was calculated as follows: 1+ (weak)=less than 10%; 2+ (moderate)=11–50%; and 3+ (strong)= more than 50% tumor cells stained positive. The χ2-test, Fisher’s exact test, and SPSS version 17 were used.Twenty-one (36.2%) and 52 (89.6) BPH and PAC specimens showed positive staining for AMACR, in contrast to 39 (67.2%) and 46 (79.3) BPH and PAC specimens for COX-2. AMACR is more sensitive and specific for PAC and more expressed in patients with a low Gleason score, whereas COX-2 is more expressed in patients with a high Gleason score. For both markers, a significant correlation was obtained between the degree of staining and the staging of the tumor as well as between Gleason score and COX-2 staining.Early detection can be made by estimation of AMACR antibody, and treatment must be focused more on AMACR than on COX-2 inhibitors.