Although genetic alterations, including mutations and amplification of MITF, are found in melanoma samples [4, 46, 48, 49], fluctuating MITF activity in melanoma cells is rather due to microenvironmental cues, critical epigenetic states and modifications of upstream signaling pathways [7, 8, 10, 79, 104–138]. The gene discussed is MITF; the disease is melanoma.