Monkeypox (MPX) is a human zoonotic disease due to Monkeypox virus. Morbidity and mortality are lower than in other Orthopox virus diseases, in particular smallpox. MPX is an endemic disease of Western and Central Africa. However, a multi-country outbreak is currently taking place in many non-endemic countries. The clinical and epidemiological characteristics of this epidemic appear peculiar, with significant differences compared to those of the endemic areas. In particular, it predominantly affects males having sex with males, and the route of sexual transmission appears to be particularly frequent. This has led to considerable media interest and concern among the population. Dermatologists are likely to be consulted frequently during the outbreak, especially for the differential diagnosis. Indeed, although MPX can affect various organs, the skin is constantly involved. Since the skin rash have different stages of development, MPX should be differentiate from several, common skin diseases, also because the systemic symptoms can be variable and of different severity. Therefore, dermatologists must be aware of the clinical characteristics of the disease and its management.