The majority of renal neoplasms can be distinguished on the basis of histologic examination alone; however, there are morphologic similarities between clear cell renal carcinoma and chromophobe cell carcinoma, as well as between the granular/eosinophilic variants of these tumors and renal oncocytoma. Only a limited number of histochemical markers are available to aid in the differential diagnosis of these neoplasms. Hale's colloidal iron usually yields strong, diffuse cytoplasmic staining of chromophobe cell carcinomas whereas clear cell carcinomas are generally negative; however, interpretation of this stain is not always straightforward. By immunohistochemistry, vimentin is detectable in most clear cell carcinomas and is absent from most chromophobe cell tumors and oncocytomas, but reliance on a single antibody can be misleading. In this report we examine the use of commercially available monoclonal antibodies to RCC and CD10 in the differential diagnosis of common renal tumors. Eighty-five percent of clear cell carcinomas (53 of 62) had detectable surface membrane staining for RCC, and 94% (58 of 62) were positive for CD10. Papillary carcinomas were likewise strongly positive for RCC and CD10 in nearly all cases (13 of 14 each). In contrast, all 19 chromophobe cell carcinomas examined were completely negative for surface membrane staining with both of these markers. Oncocytomas were also negative for RCC (0 of 9), but CD10 was detectable in some cases (3 of 9). These results suggest that the presence of surface membrane staining for RCC and CD10 may be used to confirm a diagnosis of suspected clear cell or papillary renal carcinoma. Chromophobe cell carcinomas should be negative for both markers. The absence of RCC staining may also be helpful in the diagnosis of renal oncocytoma.