The PAX3 transcription factor is critical for the proper development of neural crest lineages including melanocytes. These cells show continued PAX3 expression from formation to differentiation. While many expression, misexpression and mutation studies clarify the importance of PAX3 in melanocyte development, less well understood, and more perplexing, is the continued PAX3 expression in the adult skin. In this article we explore the multiple roles of PAX3 in melanocyte genesis, and draw on evidence from expression in developing melanoblasts, adult melanocytes and melanocyte stem cells. From this, we present a more encompassing theory that PAX3 is a key regulator of the myriad steps in melanocytic cell determination. These roles may be accomplished by differential association with cofactors, via alternate transcripts or posttranslational protein modification(s). In light of the plethora of information gleaned from development we then consider its roles in melanoma and provide here a comprehensive consideration of the significance of PAX3 expression in melanoma. PAX3 and Pax3 indicate human and mouse transcription factors respectively.