In the current issue, two articles highlight the impact of melanocyte transcription factor (MITF) on melanoma development. In the first, Lister et al. reveal in vivo proof of MITF directly regulating tumor development in BRAF(V600E) melanomas. In the second, Sturm et al. present a clinical trial that emphasizes the importance of the recently discovered E318K MITF germline mutation in patients with multiple primary melanomas.