Von Hippel-Lindau (VHL) disease is an autosomal dominant disease that produces a variety of tumors and cysts in the central nervous system and visceral organs, including renal cell carcinoma (RCC). RCC in patients with VHL disease does not frequently metastasize, therefore, the response to treatment and prognosis of metastatic RCC developed in patients with VHL disease has not been reported. Sunitinib is an oral, multitargeted receptor tyrosine kinase inhibitor with antiangiogenic and antitumor activity. Here, we report on four patients with metastatic RCC in VHL disease who received sunitinib and achieved partial responses that have lasted for a prolonged period of time.