Background: Differentiating oncocytoma from its renal cell. particularly chromophobe RCC, carcinoma (RCC) mimics. can be difficult, especially when limited tissue is available for evaluation. This Study presents a panel of markers that are readily available, easy to use, and useful for differential diagnoses of renal tumors. Design: A renal cell neoplasm tissue microarray was constructed including oncocytoma (n = 30), chromophobe RCC (it = 18). conventional RCC (n = 64), papillary RCC (n = 50), and benign renal tissues (n = 31). CK7, CD10, epithelial membrane antigen, renal cell carcinoma marker (RCCma), vimentin, and endogenous avidin-binding activity (EABA) were studied. An Automated Cellular Imaging System, was used to quantify the staining intensity. Result: EABA was positive in 97% of oncocytoma, 26% of conventional RCC and 35% of papillary RCC with granular/eosinophilic (G/E) features and 6% of chromophobe RCC. EABA wits negative in RCC without G/E features. Vimentin and RCCma were positive in most RCC with G/E features (conventional, 78% and 71%; and papillary, 85% and 76%, respectively), and negative in oncocytoma. Vimentin was also negative in chromophobe RCC. CK7 was positive in Lip to 81% of papillary RCC and 63% of chromophobe RCC, and essentially negative in conventional RCC and oncocytoma. Conclusions: EABA is an excellent marker for oncocytoma, which can be useful in differentiating oncocytoma from chromophobe RCC. A panel of EABA, vimentin, and RCCma markers can be useful in discerning oncocytoma from RCC with G/E features. Vimentin can be useful in discriminating chromophobe RCC from papillary or conventional RCCs.