Chromophobe renal cell carcinoma and renal oncocytoma have overlapping morphologic, histochemical, immunohistochemical, and ultrastructural features; however, their distinction is critical inasmuch as the former neoplasm has a malignant potential and the latter is widely believed to be a benign tumor. In this study, we investigated the potential utility of nuclear features in differential diagnosis. Nuclear contours, nuclear chromatin pattern, binucleation or multinucleation, pleomorphism, and mitotic activity were assessed semiquantitatively in routine H&E-stained sections from 16 cases of chromophobe renal cell carcinoma and 21 cases of renal oncocytoma. All cases of chromophobe renal cell carcinoma were found to have wrinkled, "raisinoid" nuclei in varying proportions, whereas all renal oncocytomas had predominantly round, relatively uniform nuclei. Binucleation or multinucleation was significantly more common in chromophobe renal cell carcinoma. Nuclear chromatin tended to be coarser in chromophobe renal cell carcinoma and nucleoli were seen more commonly in renal oncocytoma. Of the renal oncocytomas, 19% had distinct foci of "degenerative" nuclear atypia with pleomorphism. This type of atypia was absent in chromophobe renal cell carcinoma. Our study shows that in association with the well-described cytoplasmic and architectural features, nuclear parameters are valuable discriminants between chromophobe renal cell carcinoma and renal oncocytoma. Frequent binucleation and "raisinoid" nuclei with perinuclear halos, resulting in "koilocytoid atypia," is highly characteristic of chromophobe renal cell carcinoma.