The incidence of native kidney renal cell carcinoma (RCC) in renal transplant recipients is 15 times higher than the general population. These tumors are often found incidentally when imaging is performed for another indication. At that stage tumors are usually small and asymptomatic but it is possible that they may escape detection until a more advanced stage. Early stage RCC can be treated with radical nephrectomy but the treatment of advanced RCC may be more complicated and is associated with a poorer prognosis. RCC in context of renal transplant presents a special therapeutic challenge; balancing treatment of a potentially lethal malignancy in a redundant organ whilst maintaining good allograft function.We describe 2 cases of advanced renal cell carcinoma of native kidneys in renal transplant recipients and present our experience with sirolimus as a dual immunosuppressive and anti-tumor agent.