From 1.5% to 9.0% of prostatic needle biopsy specimens disclose atypical small acinar proliferations (ASAPs) suggestive of malignancy, carrying an approximate 45% predictive value for cancer. We applied keratin 34 beta E12 and P504S monoclonal immunostains to 93 cases that were judged as ASAP after H&E staining alone. Forty-one ASAP foci survived recutting for both immunostains. Three urologic pathologists independently assigned post-keratin 34 beta E12 diagnoses of cancer, ASAP, high-grade prostatic intraepithelial neoplasia, or benign and then reviewed P504S slides and assigned final diagnoses. Eight foci (20%) were resolved unanimously after keratin 34 beta E12 staining; 18 (44%) were resolved by 1 or 2 evaluators and 29 (71%) by at least 1. According to whether post-keratin 34 beta E12 ASAP designation was given by 3, 2, or 1 evaluator(s), P504S immunostaining unanimously resolved an additional 5 (12%), 10 (24%), or 23 (56%) of 41 ASAP foci and cumulatively, 31 foci (76%). Among 35 men (excluding 6 with cancer in other cores of the original biopsy), these immunostains could have permitted cancer diagnosis in 11 (31%), without repeated biopsy. Thus, the consensus diagnosis rate improved from poor to good after supplementing 34 beta E12 immunostaining with P504S.