Abstract. The aim of this study was to evaluate the status of HER2 protein expression in patients with renal cell carcinoma (RCC) and to determine its prognostic significance. A total of 42 paraffin-embedded tumor tissues and 42 additional corresponding adjacent normal tissues from RCC patients were randomly collected and studied using immunohistochemistry (IHC). Protein samples of 6 fresh specimens from tumor and adjacent normal tissues obtained during surgery were extracted and tested using western blotting to confirm the IHC results. Of the 42 tumor tissues and adjacent normal tissues tested, IHC showed that 7 tumors (16.67%) and 33 adjacent normal tissues (78.57%) expressed the HER2 protein. In addition, results of the western blotting revealed weak HER2 reactivity in primary tumor cells in two of 6 specimens obtained during surgery. All 6 normal tissues showed positive expression, which was in accordance with the outcome of IHC. In conclusion, HER2 is frequently expressed in normal renal tissues and rarely expressed in RCC tissues. Furthermore, the HER2 status of normal tissue is negatively correlated with that of the RCC tissues (r=-0.410, P=0.007) and the TNM stage (r=-0.246, P=0.027), suggesting that HER2 is involved in RCC oncogenesis.