Malignant melanoma is the most deadly form of skin cancer and its incidence is steadily increasing worldwide. The plasma membrane in melanoma cells possesses a variety of ion channels, so its profile is thought to lead to a novel target for medical treatment for malignant melanoma. Here we showed that human melanoma G-361 cells expressed the epithelial Na(+) channel delta subunit (ENaC delta), which is largely unknown in physiological and pathological functions in non-neuronal tissues. Expression analyses at the level of mRNA clearly revealed that ENaC delta transcript was strongly expressed in human melanoma cells using reverse transcription-polymerase chain reaction and cell-based in situ hybridization techniques. Other ENaC subunits (alpha, beta, and gamma) were also distributed in human melanoma cells. In addition, human melanoma cells possessed an abundant expression of ENaC delta protein by immunocytochemistry. These results provide an attractive target for drug development of malignant melanoma.