Renal neoplasms comprise several distinct clinicopathologic entities with potential prognostic and the rapeutic differences. Although careful morphologic examination using sections stained with hematoxylin and eosin will allow for the correct diagnosis in the majority of cases, there is sufficient overlap between several entities such that ancillary techniques may be necessary to arrive at the correct diagnosis. In routine diagnostic surgical pathology practice of renal tumors, immunohistochemistry is the foremost ancillary technique. Using an approach based on common histologic patterns (tumors with clear cytoplasm, granular cytoplasm, tubulopapillary architecture, spindle cell morphology, small round-cell morphology, and infiltrating poorly differentiated carcinoma), we will discuss the utility of immunohistochemistry in the differential diagnosis of renal neoplasms. In recent years, needle biopsies from renal masses are being increasingly performed. In these small biopsies, the entire range of cytoarchitectural features that are generally necessary to make a diagnosis may not be fully appreciated. Immunohistochemistry may be helpful in this setting to narrow the differential diagnosis or to arrive at a definitive diagnosis. Finally, the use of immunohistochemistry for the confirmation of metastatic renal cell carcinoma presenting at distant sites will be discussed. Panels of immunohistochemical stains are proposed for different settings, including renal cell carcinoma (RCC) marker, CD10, and vimentin to suggest renal origin of a metastatic tumor, and markers to aid in subclassification of RCC, including parvalbumin and c-kit for chromophobe RCC, and cytokeratin 7 and alpha-methyl-acyl-CoA racemase for papillary RCC.