AbstractMicrophthalmia‐associated transcription factor (MITF) is a nodal point in melanoma transcriptional network that regulates dozens of genes with critical functions in cell differentiation, proliferation and survival. Highly variable MITF expression levels exist in tumor cell subpopulations conferring marked heterogeneity and plasticity in the tumor tissue. A model has been postulated whereby lower MITF levels favour cell invasion and suppress proliferation, whereas high levels stimulate differentiation and proliferation. Additionally, MITF is considered to be a prosurvival gene and a lineage addiction oncogene in melanoma. Herein, we review how MITF expression may affect the melanoma phenotype with consequences on the survival, invasion and metastasis of melanoma cells, and we discuss the research challenges.