Melanoma is an aggressive tumor with invasive and metastatic potential, frequently exhibiting multidrug resistance mechanisms. In our continuous search for antimelanoma molecules, we have identified some effective marine compounds capable of not only inducing cell death, but also of sensitizing chemoresistant tumor cells to clinically used anticancer drugs. In this report, the cryptophyte Rhodomonas salina (Wislouch) D.R.A.Hill & R.Wetherbee, Pyrenomonadaceae, was chemically investigated in order to identify pigments efficiently inhibiting melanoma cells proliferation. All pharmacological tests were performed on A2058 cells expressing the oncogenic BRAF V600E mutation and resistant to dacarbazine treatment. Flash chromatography of R. salina ethanol extract led to purification of alloxanthin and crocoxanthin, which showed significant antiproliferative activity against A2058 cells, exhibiting IC50 = 29 and 50 μM, respectively. These carotenoids promoted growth inhibition, decreased cell migration, and induced apoptosis and sub-G1 cells accumulation after 72 h of treatment. In addition, alloxanthin potentiated the cytotoxic activity of vemurafenib (a BRAF inhibitor) and restored the sensitivity of A2058 cells to dacarbazine treatment.