Renal oncocytoma (RO) is a distinctive neoplasm with a well-recognized gross and cytoarchitectural appearance. However, on some occasions, it may show uncommon, atypical, or worrisome gross and microscopic features potentially generating diagnostic difficulties. We herein review the oncocytoma variant characterized by a significant intraneoplastic xanthomatous reaction that produces a variegated macroscopic appearance. This feature may pose a genuine diagnostic problem with conventional (clear cell) renal cell carcinoma (RCC) because this reaction creates a departure from the typical uniform, tan-brown appearance of oncocytoma. The microscopic presence of foamy macrophages in RO may potentially lead to diagnostic difficulties with tumors exhibiting eosinophilic cells and significant infiltration for lipid-laden foamy macrophages such as cystic RCC, unclassified RCC rich in foamy macrophages, the solid variant of papillary RCC with oncocytic features, post-neuroblastoma RCC, succinate dehydrogenase-deficient RCC, mucinous-poor tubular and spindle cell carcinoma, and the oncocytic variant of the epithelioid angiomyolipoma. In conflictive cases, an immunohistochemical panel should help to solve the diagnostic problem. Therefore, the presence of abundant foamy macrophages should not dissuade the pathologist from establishing a diagnosis of RO. Prominent xanthomatous reaction despite its low frequency (4.3%) can be considered an additional feature of RO. Thus, RO should be added to the list of renal tumors that can show a significant reaction of lipid-laden foamy macrophages. Besides, Gamna-Gandy bodies can be present in this tumor.