 Melanocytes can de-differentiate into neural crest cell, NCC, like states during metastatic melanoma progression. Here the authors compared DNA methylation profiles of NCCs and melanocytes, as well as primary and metastatic patient tissues, and identified that DNA methylation changes of NR2F2 isoform2 influence cell state transitions and melanoma metastatic spread. This article was authored by Veronica de Vellos, Claudia D. Lovell, Richard von Itter, and others.