ObjectiveTo investigate the clinical features, differential diagnosis and treatment for chromophobe cell renal carcinoma (CRCC) and renal oncocytoma. MethodsFrom December 2009 to May 2013, we selected 41 cases of CRCC and 22 cases of renal oncocytoma, retrospectively analyzed their clinical features, ultrasonography and CT findings and performed immunohistochemical staining for CK7, CD10, PAX-2, and Ksp-cadherin. ResultsCRCC could be associated with lower back pain or hematuria, and renal oncocytoma generally did not have clinical symptoms. Ultrasonography and CT examination were not specific for the differentiation between the two diseases. The expression rates of CK7, CD10, PAX-2, and Ksp-cadherin in CRCC were 66% (21/32), 22% (7/32), 23% (3/13) and 93% (14/15), respectively. In patients with oncocytoma, 7% (1/15) were positive for CK7, 7% (1/15) were positive for CD10, 86% (13/15) were positive for PAX-2, and 31% (4/13) were positive for Ksp-cadherin. Pearson chi-square analysis was performed with a significant P value set at <0.05. The results of CK7(-)CD10(-)PAX-2(+) and CK7(-)CD10(-)Ksp-cadherin(-) immunohistochemistry were integrated, which also showed the differences. ConclusionThe combination of CK7(-)CD10(-)PAX-2(+) and CK7(-)CD10(-)Ksp-cadherin(-) immunohistochemistry may be useful for differentiating between CRCC and oncocytoma. Combined with imaging examination, it can further improve the differential diagnosis of the two diseases.