Imatinib mesylate (Gleevec, formerly STI571; Novartis Pharmaceuticals, Basel, Switzerland), is a selective inhibitor, targeting Abl as well as c-Kit and the platelet-derived growth factor receptor. Imatinib demonstrated significant activity in patients with metastatic melanoma harboring genetic c-Kit aberrations, with an overall response rate of 29% (J Clin Oncol 2011;29:2904-9) Regorafenib (BAY 73-4506) is a novel, orally active, diphenylurea multikinase inhibitor of VEGFR1-3, c-KIT, TIE-2, PDGFR-β, FGFR-1, RET, RAF-1, BRAF and p38 MAP kinase. Regorafenib provide a significant improved PFS and OS in patients with GIST and colorectal cancer, respectively (Lancet 2013; 381: 295-302, Lancet 2013; 381: 303-12). Especially, inhibitory activity of regorafenib is most effective in c-kit mutated tumors. Therefore, regorafenib has a chance to significant activity in melanoma with c-kit mutations. However, no clinical trials have been published for regorafenib in the patients with melanoma who harbor c-Kit mutations.