Sunitinib is approved for the treatment of metastatic renal cell carcinoma (RCC). No data are available on sunitinib use specifically in patients with significantly impaired renal function. We evaluated the safety and efficacy of sunitinib in patients with advanced RCC and Grade 4 renal function impairment. Four patients had a calculated creatinine clearance of 15 - 29 ml/min/1.73 m2 prior to initiation of sunitinib. Three patients tolerated treatment well with no renal toxicity: 2 received 17 and 5 cycles of sunitinib at full dose, while 1 received 5 cycles with a dose reduction due to myelotoxicity. We observed one partial response and two patients had stable disease for 24 and 4 months, respectively. The 4th patient had a creatinine clearance of 18 ml/min/1.73 m2 and had treatment discontinued during the first cycle due to poorly controlled hypertension and deterioration of his renal function. We conclude that sunitinib can be administered to the majority of patients with RCC and significant renal function impairment.