Recently, genetic alterations activating the receptor tyrosine kinase KIT have been shown in some types of melanoma. KIT mutations can be successfully targeted by approved drugs in other cancers. Emerging evidence suggests that melanomas with KIT activation may also respond to KIT inhibitors that are already in clinical use. If confirmed in ongoing clinical trials, this experience would underscore the importance of recognizing the biological diversity among melanomas, representing a first decisive step toward the individualized and mechanism-based treatment of melanoma.