Renal cell carcinoma (RCC) is a histologically diverse disease, with variable and often unpredictable clinical behavior. The prognosis worsens dramatically with the onset of clinical metastasis, and current regimens of systemic therapy yield only modest benefits for metastatic RCC. Gene expression profiling is a promising technique for refining the diagnosis and staging of RCC, as well as for highlighting potential therapeutic targets. We review the recent advances in expression profiling of RCC and discuss the clinical and biological insights obtained from these studies.