To evaluate the physiological role of up-regulation of expression of different members of the DEG/ENaC family in melanoma cells, we performed a comparative analysis of expression of the ACCN2, ACCN1, ACCN3, ACCN4, SCNN1A, and SCNN1G genes in non-glabrous primary and metastatic melanoma cells and in human healthy skin samples from the TCGA SKSM and GTEX databases. This evidence concerns the gene ASIC2 and metastatic melanoma.