Increasing evidence indicates that Notch signaling contributes to physiologic processes, including development, differentiation and tumorigenesis, either as a tumor promoter or suppressor depending on the cellular context, level of expression and cross‑talk with other signaling systems. Notch signalling has been implicated in the regulation of self‑renewal of adult stem cells and differentiation of precursors along a specific cell line in normal embryonic development and organogenesis. There is also evidence that signaling through Notch receptors regulates cell proliferation and cell survival in several types of cancer including malignant melanoma, with opposing results depending on the tissue context. Tumor progression/metastasis of malignant melanoma are complicated processes that require multiple cellular events, including cell proliferation, survival, migration and invasion. Notch signaling appears to be a promising system for new therapeutic targets for the treatment of melanoma and perhaps the prevention of melanoma metastasis.