Adenocarcinoma of the prostate measuring <1 mm in needle core tissue can present a diagnostic challenge. The α-methylacyl-CoA racemase (AMACR) immunostain, a marker of neoplastic prostatic epithelial cells, may be used to evaluate these limited tumor cases, in needle biopsy, with a reported sensitivity ranging to a low of 80%. The use of the ERG immunostain in evaluating prostate cancer is becoming more common, but the utility of this marker in direct comparison with AMACR has not been examined. The purpose of our study was to investigate whether the ERG immunostain adds diagnostic value to AMACR expression in evaluating untreated prostate cancer foci measuring <1 mm in core needle biopsy. We identified 129 blocks from 113 patients with continuous tumor foci measuring <1 mm on core needle biopsy. ERG and AMACR immunostaining analyses were performed on serial sections from the blocks, and expression was assessed by intensity and proportion scores assigned to each stain. Sixty-five of the selected blocks from 63 patients retained tumor foci measuring <1 mm after obtaining deeper sections. Of these 65 tumor foci, 36 were positive for AMACR alone, 28 were positive for AMACR and ERG, and 1 was positive for ERG alone. AMACR had a sensitivity of 99%, and ERG had a sensitivity of 45%. Most cases displayed strong AMACR expression, and only 7 of 65 foci (11%) exhibited weak or negative AMACR expression. Of these 7 foci with weak or negative AMACR expression, only 2 foci were ERG positive. This is the first study to our knowledge that examines the diagnostic utility of ERG expression in comparison with AMACR expression in minimal usual acinar adenocarcinoma of the prostate in core needle biopsy. Our findings suggest that AMACR should be the first-line positive marker for confirmation of a diagnosis of minimal adenocarcinoma of the prostate, when needed. ERG immunohistochemistry is potentially indicated only in uncommon cases of minimal adenocarcinoma when AMACR staining is negative or weak, and in these cases ERG is informative in only a minority (29%) of cases. Evidence-based utilization of diagnostic markers, without their routine overutilization, such as ERG expression in minimal adenocarcinoma, that do not provide added diagnostic value in most cases, is an important principle in application of immunohistochemistry in this era of cost-consciousness.