Receptor tyrosine kinases (RTKs) play key roles in the initiation and progression of human skin cancers, yet the importance of some RTKs remains poorly understood. In this issue, Sensi et al. provide new insights into the expression and function of the RTK, Axl, in melanoma. The investigators show that Axl is frequently expressed in melanoma cell lines, particularly mutant NRAS-harboring lines, and that Axl activation by its ligand, Gas6, probably occurs via both autocrine and paracrine mechanisms. Gene signatures from Axl-expressing cell lines are similar to published signatures from poorly differentiated tumors displaying high metastatic potential. Functionally, Axl was required for the invasive and migratory properties of Axl-expressing melanoma cell lines. These data emphasize that targeting the Gas6-Axl signaling axis should be investigated as a strategy to inhibit prometastatic properties in poorly differentiated melanomas.