Multiple therapeutic options for renal tumors that are now available have put pathologists under increasing pressure to render diagnosis on limited material. Results on biopsies by hematoxylin and eosin (H&E) have historically not been encouraging. Currently, multiple immunohistochemical markers with differential expression in these renal tumors are available. We studied the utility of such markers on needle biopsies that were obtained ex vivo. After nephrectomy, two 18-guage cores were obtained and processed routinely. Expressions of carbonic anhydrase (CA) IX, CD117, α-methylacyl-CoA racemase (AMACR), cytokeratin 7 (CK7), and CD10 were evaluated. Results, with or without immunostaining, were compared with the final nephrectomy diagnosis. We studied 145 tumors, including 119 renal cell carcinomas (83 clear cell, 18 papillary, 14 chromophobe, and 4 type unclassified), 11 oncocytomas, and 15 miscellaneous tumors. Adequate evaluable material was present in 123 (85%) cases. In such biopsies, 81% of cases were correctly classified by H&E alone, with correct diagnosis in 90% of cases in the most common tumor subtypes (clear cell, papillary and chromophobe renal cell carcinoma, and oncocytoma). By adding immunostains, the accuracy was 90% overall and 99% among the 4 most common subtypes. The following extent and patterns of immuneexpression were highly useful in the diagnoses: diffuse, membranous CAIX expression in clear cell renal cell carcinoma, diffuse positivity for AMACR in papillary renal cell carcinoma, distinct peripheral cytoplasmic accentuation for CD117 in chromophobe renal cell carcinoma, widespread and intense positivity for CK7 in chromophobe and papillary renal cell carcinoma, and diffuse membranous reactivity in clear cell and patchy/luminal in papillary renal cell carcinoma for CD10. In conclusion, utilizing immunostains improves classification of renal tumors on needle biopsy, which may be of particular help for pathologists with limited experience. Both extent and patterns must be considered for a definitive diagnosis.