Objective To determine the frequency of HER2 genetic abnormalities in renal cell carcinoma (RCC) and hence assess the potential suitability of Herceptin TM immunotherapy. Patients and methods Tumours from 27 patients with RCC were assessed; all patients had undergone nephrectomy. Benign renal tissue from the nephrectomy specimens was studied in seven patients. Gene ampli®cation was assessed using¯uorescent in-situ hybridization, and protein over-expression using immunohistochemistry. Results Twenty-four patients had clear cell renal carcinoma, two had papillary renal carcinoma and one a sarcomatoid variant carcinoma. There was no HER2 ampli®cation in the tumours or the benign renal tissue. Polysomy 17 was detected in 11 of 27 tumours (41%) and increased HER2 copy number in seven (26%). Both polysomy 17 and increased HER2 copy number were absent in the benign renal tissue. Three tumours (11%) and six of the seven benign renal tissue samples over-expressed the HER2 protein. Conclusions HER2 ampli®cation is absent and protein over-expression uncommon in RCC. This casts doubt on the suitability of Herceptin TM in the treatment of RCC.