Pigment cells that differentiate in the vertebral skin arise from the neural crest (NC), a transitory structure formed at the dorsal borders of the neural plate and which gives rise to migratory cells of multiple fates. How NC cells become committed to the melanocytic lineage and what factors control the survival, proliferation and differentiation of melanocyte precursors remain largely unknown. These issues are of great importance for understanding the mechanisms of several pigment cell pathologies including melanomas. Recent in vivo and in vitro analyses of the fate of single NC cells have indicated that multipotent cells yield melanocyte precursors that become spatially and temporally segregated from other, non melanogenic, NC-derived cell types. The proper development of subsets of NC precursors is governed by environmental local cytokines acting in a paracrine manner. The conjunction of recent studies in mammals and birds reviewed here focuses on the action of endothelin 3 in controlling both the emergence and the maintenance of the NC-derived melanocyte phenotype.