Objective To investigate the expression and diagnostic significance of CK7 and S100A1 in chromophobe renal cell carcinoma (chRCC) and renal oncocytoma. Methods The expression of CK7 and S100A1 in 22 cases of chRCC and 20 cases of renal oncocytoma was determined by immunohistochemical staining. Results Positive expression of CK7 was observed in 20 cases (90.9%) of chRCC and 2 cases (10.0%) of renal oncocytoma (P=0.000). Positive expression of S100A1 was observed in 14 cases (63.6%) of chRCC and 19 cases (95.0%) of renal oncocytoma (P=0.003). Conclusion Immunohistochemical staining of CK7 and S100A1 may be helpful for differential diagnosis of chRCC and renal oncocytoma.