Melanoma is an aggressive tumor with advanced disease characterized by widespread metastatic lesions and the tumor has traditionally been resistant to most forms of treatment. Indeed, metastatic melanoma has a very poor prognosis with a median survival time of 8-9 months and an estimated 3-year survival rate of less than 15%. Recent advances in our understanding of the genetic profile of melanoma cells and the molecular factors that drive malignant transformation have resulted in the identification of numerous new therapeutic targets. KIT is an established therapeutic target in cancers with activating mutations of KIT, such as gastrointestinal stromal tumors (GIST), and considerable efficacy has been achieved with various small molecule inhibitors of KIT including imatinib mesylate. Nilotinib is an inhibitor of ligand-induced PDGFRα and PDFGRβ kinase activity and autophosphorylation of constitutively activated KIT harboring exon 13 or exon 11 mutations (IC50 values of 0.2 and 0.027 μmol/L, respectively), with efficacy comparable to that of imatinib. We report a case of non-kit mutated metastatic vaginal melanoma showing impressive response to nilotinib.