Despite the recent spectacular improvements in targeted melanoma treatment (i.e., BRAF (B-Raf Proto-Oncogene, Serine/Threonine Kinase) and MEK (mitogen-activated protein kinase kinase enzymes) inhibitors or immunotherapies), more than half of the patients will be in treatment failure and chemotherapy may still be important in the palliative treatment of refractory, progressive, and relapsed melanoma [4,5]. This evidence concerns the gene MARK2 and melanoma.