We demonstrate that, in addition to promote melanoma development, Mothers against decapentaplegic homolog 3 (SMAD3), Baculoviral IAP repeat‐containing protein 3 (BIRC3), and Sodium/hydrogen exchanger 5 (SLC9A5) also support relapse since they promote both BRAFi‐resistance and tumor growth capability of persister cells. The gene discussed is SLC9A5; the disease is melanoma.