BACKGROUND: The histologic classification of renal cell carcinoma (RCC) is based on the cytoarchitectural features, yet sometimes this requires correlation with the immunophenotype. Alpha-methylacyl-CoA racemase (AMACR) and claudin-7 have recently been introduced as useful markers that are frequently expressed in papillary RCC (PRCC) and chromophobe RCC (ChRCC), respectively. The aims of this study are to evaluate the expressions of AMACR and claudin-7 in RCCs and to investigate whether they are helpful for making the histological classification of RCCs. METHODS: Immunohistochemistry for CD10, RCC marker, cytokeratin (CK)7, CD117, AMACR and claudin-7 was performed for 104 RCCs, and these consisted of 54 clear cell RCCs (CCRCC), 26 PRCCs and 24 ChRCCs. RESULTS: For diagnosing PRCC, the sensitivity and specificity of AMACR were 92.3% and 71.8%, respectively, and using AMACR(+)/CK7(+), the specificity was increased by 23.1% to 94.9%. For diagnosing ChRCC, the sensitivity and specificity of claudin-7 were 91.7% and 78.8%, respectively, and using claudin-7(+)/AMACR(-), the specificity was significantly improved (to 96.3%). For diagnosing CCRCC, CK7(-)/claudin-7(-)/CD117(-) was the most useful immunohistochemical panel (sensitivity, 96.3%; specificity, 98%). CONCLUSIONS: AMACR and claudin-7 are helpful markers for the histologic classification of RCCs, and their diagnostic utility is strengthened when they are used as an immunohistochemical panel, AMACR(+)/CK7(+) for PRCC, claudin-7(+)/AMACR(-) for ChRCC and CK7(-)/claudin-7(-)/CD117(-) for CCRCC.