The crucial role of the embryonic neural crest signaling for melanoma progression is underlined by a neural crest related gene signature. Since non-canonical Wnt signaling pathways that frequently involve Wnt5a are complementary strong contributors to the invasive behavior of melanoma cells, we believe in a context dependent, plastic effect of distinct Wnt ligands and their corresponding receptorsor adaptors. Here, WNT5A is linked to melanoma.