In this study we provide evidence, that the soluble form of Lyve-1 derived from macrophage-like cells significantly decreases melanoma cell proliferation by functioning as a decoy receptor for LMW-HA even though LYVE-1+ macrophages display a M2-like phenotype with a strong co-expression of the M2-markers CD206 and CD163. This evidence concerns the gene LYVE1 and melanoma.