Histologic subtyping of RCC has been shown to be of prognostic value; therefore, it is important to classify malignant epithelial tumors of the kidney correctly and also to differentiate them from benign ones. Overlapping morphologic features of renal tumors sometimes make histologic subtyping difficult. The accurate diagnosis and classification of RCC are based on cytoarchitectural features and require correlation with immunophenotype and cytogenetic characteristics. RCC Ma and CD10, two markers with relative renal specificity, have been used to confirm a diagnosis of suspected RCC and can facilitate the accurate diagnosis of metastatic RCC, in particular, in FNA. Although CCRCC and PRCC share most immunomarkers, CK7 and AMACR expression can be helpful in the differential diagnosis of challenging histologic variants of the two. In addition, E-cadherin aids in the distinction between types 1 and 2 PRCC. Useful markers in the differential diagnosis between ChRCC and CCRCCare CK7, RCC Ma, CD10, VIM, CD117, parvalbumin, and E-cadherin. We propose CK7/CK20/CD15 as a useful primary immunopanel to differentiate ChRCC from ONC reliably.