Objective: Renal oncocytoma (RO) and chromophobe renal cell carcinoma (ChRCC) originate from the same cell origin, that is, the intercalated cells of the collecting duct. In most cases, there are clear morphologic differences between RO and ChRCC; however, in some instances, overlapping features may be encountered and the differentiation between the two entities becomes difficult. Several immunohistochemical markers with different expression patterns in ChRCC and RO have been described to rule out this dilemma. Materials and Methods: About 47 primary renal neoplasms that had been diagnosed as RO or ChRCC were submitted for immunohistochemical staining of amylase α‑1A (AMY1A), MOC 31, and CD 82. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy have been analyzed. Results: AMY1A positivity was observed in all RO cases in our work with 91.7% sensitivity and 100% specificity in the diagnosis of RO. The PPV of its expression was (100%) and NPV (97.2%) with a diagnostic accuracy of 97.9%. A significant high expression of MOC 31 was observed in ChRCC compared to its expression in RO with a statistical significance (P < 0.001). In addition, we obtained 82.9% sensitivity and 91.7% specificity of MOC 31 expression in the diagnosis of ChRCC. The positive predictive value (PPV) was (96.7%), negative predictive value (NPV) (64.7%) with diagnostic accuracy (85.1%). In our studied cases, we detected positive immunoexpression of CD 82 in 10 cases (83.3%) of ChRCC. However, it was lost in all RO cases (100%). CD 82 sensitivity and specificity in differentiating ChRCC from RO were 100% and 83.3%, respectively. Conclusion: We propose MOC 31 and CD 82 as negative immunostains for RO, as these markers are commonly expressed in ChRCC. In conjunction with AMY1A strong immunopositivity in RO cases, we provide a triple panel of biomarkers (AMY1A, MOC 31, and CD 82) for the distinction between RO and ChRCC.