AIMS The common subtypes of renal tumours are conventional, papillary, chromophobe carcinoma and oncocytoma. The morphological differentiation between chromophobe carcinoma and oncocytoma may be difficult. The aim was to evaluate S100A1 as a new marker for the differentiation of the two subtypes. METHODS AND RESULTS Thirty-nine tumour samples [nine clear cell renal cell carcinomas (RCCs), six papillary RCCs, nine chromophobe RCCs and 15 oncocytomas] were studied. The protein expression of S100A1 was evaluated by immunohistochemistry. The gene expression of S100A1 was analysed by reverse transcriptase-polymerase chain reaction. Nine oncocytomas showed strong immunoreactivity for S100A1. Four oncocytomas were scored as moderate and one as weak reactivity. In total, 14/15 (93%) of oncocytomas were considered to be immunopositive. In contrast, all nine chromophobe RCCs were considered to be immunonegative. There was a significant difference in the positive percentages of staining of S100A1 between these two subtypes (P < 0.01). S100A1 immunoreactivity was observed in 6/9 clear cell and 4/6 papillary carcinomas. The results of S100A1 gene expression corresponded well with the results of immunohistochemistry. CONCLUSION S100A1 may be a potentially powerful marker to differentiate the chromophobe RCC from renal oncocytoma.