Here we showed that Mgrn1 knockdown in normal melanocytes and melanoma cells induced a phenotype characterized by: (i) cell morphology changes with increased size, higher number of dendrites, longer protrusions and higher melanin content, (ii) impaired cell motility and higher adhesion to collagen matrices, (iii) abnormal cell cycle progression with increased percentage of cells in S phase, and (iv) decreased genome stability with accumulation of DNA damage. This evidence concerns the gene MGRN1 and melanoma.