In humans and other species, Notch‑signaling is of critical importance for carcinogenesis in several organs, including the skin. Interestingly, Notch‑signaling appears to exert opposite roles in skin carcinogenesis as compared to carcinogenesis in other tissues. While the Notch1 receptor (Notch1) acts as a proto‑oncogene in most tissues, it has been shown that Notch1 deletion in epidermal keratinocytes causes skin carcinogenesis. Recent results indicate that loss of Notch1 is not involved in the initiating event of multistage skin carcinogenesis, but acts as a skin cancer‑promoting event. Moreover, recent findings underline the importance of multiple other factors, including the microenvironment, for Notch signaling in skin carcinogenesis. It can be speculated that pharmacologic modulation of Notch signaling may be an interesting target for the prevention and therapy of skin cancer.