AMACR is an essential enzyme in the b-oxidation of branched-chain fatty acids. High expression of AMACR protein is found in prostate adenocarcinoma but not in benign prostate tissue by immunohistochemical staining in paraffin-embedded tissue. The expression of AMACR is also detected in prostate premalignant lesions, such as prostate intraepithelial neoplasia (PIN). The p63 protein, a homologue of the tumor-suppressor p53, is highly expressed in the basal or progenitor layer of many epithelial tissues. P63 is detected in prostate basal cells in normal prostate glands and PIN. However, it is negative in prostate adenocarcinoma. Thus p63 is useful as a differential marker for benign prostate glands and adenocarcinoma (negative marker). The combination of AMACR and p63 may be extremely useful for diagnosing PIN and small focus adenocarcinoma, especially in difficult cases and cases with limited tissues. AMACR stains cytoplasm in prostate adenocarcinoma and PIN while p63 stains basal cell nuclei in PIN and benign prostate gland.