Retrospective and molecular biologic data suggest that sunitinib may be effective in patients with non-clear cell renal cell carcinoma (nccRCC). Eligibility criteria included advanced nccRCC except for collecting duct carcinoma and sarcomatoid carcinoma without identifiable renal cell carcinoma subtypes. Patients were treated with 50 mg/day oral sunitinib for 4 weeks, followed by 2 weeks of rest. The primary end point was overall response rate (RR). Thirty-one eligible patients were enrolled. Twenty-four patients (77%) had prior nephrectomy. By Memorial Sloan-Kettering Cancer Center criteria, 8 patients (26%) had poor risk and 14 (45%) had intermediate risk. Twenty-two patients had papillary renal cell carcinoma (RCC), and three had chromophobe RCC. Eleven patients had partial response with a RR of 36% (95% confidence interval (CI) 19% to 52%) and an additional 17 patients (55%) had stable disease. Median duration of response was 12.7 months (95% CI 6.3–19.1 months), and median progression-free survival was 6.4 months (95% CI 4.2–8.6 months). At a median follow-up duration of 18.7 months (95% CI 13.7–23.7 months), 13 patients (42%) had died, resulting in an estimated median survival of 25.6 months (95% CI 8.4–42.9 months). Toxicity profiles were commensurate with prior reports. Sunitinib has promising activity in patients with nccRCC (NCT01219751).