The common histopathologic subtypes of renal epithelial neoplasms include conventional, or clear cell, renal cell carcinoma (RCC), papillary RCC, chromophobe RCC, and renal oncocytoma. These subtypes differ clinically and pathologically, making accurate classification important. However, this differential diagnosis can be challenging because of overlapping morphology, suggesting a potential utility for ancillary immunohistochemical markers. We used cDNA microarrays to identify candidate markers for distinguishing renal tumor subtypes. In this report we validated differential expression of three candidate markers, beta defensin-1, parvalbumin, and vimentin, and evaluated the use of this immunohistochemical panel as a potential diagnostic tool. Consistent with our cDNA microarray data, chromophobe RCCs and oncocytomas exhibited similar expression profiles: 8 of 8 examples of each subtype were immunohistochemically positive for beta defensin-1 and parvalbumin and negative for vimentin (sensitivity 100%, specificity 100%); 4 of 7 papillary RCCs were positive for beta defensin-1, parvalbumin, and vimentin (sensitivity 57%, specificity 97%); and 22 of 23 conventional RCCs were negative for beta defensin-1, parvalbumin, or both markers (sensitivity 96%, specificity 96%) as well as positive for vimentin (sensitivity 83%). The immunohistochemical panel distinguished renal tumor subtypes with greater specificity than any marker used alone. This work demonstrates that a useful panel of immunohistochemical markers can be derived from differential gene expression profiles determined using cDNA microarrays.