Mpox Virus (MPXV) is a zoonotic infectious disease first identified in 1970 in rural villages in rainforest areas of central and western Africa when smallpox was in the final stages of eradication. Since May 2022, cases and sustained transmission chains of monkeypox have been reported for the first time in countries where the disease is not endemic and without cases having direct or immediate epidemiological links to areas of West or Central Africa (travel, importation of mammals). On 23 July 2022, WHO declared monkeypox a “Public Emergency of International Concern” (PHEIC). In this paper, we report two cases of a Polymerase Chain Reaction (PCR)-confirmed MPXV infection. A 39-year-old Italian male came to our attention for a suspected herpetic infection, fever, headache, and malaise, which were followed by the development of an erythematous plaque covered by vesicles on the chin, an oval ulcer with a white peripheral border on the lower lip, and a central erosive area and three pustules on the arms and trunk. During the physical examination, cervical lymphadenopathy was also detected. PCR investigation of the patient and his partner confirmed the presence of MPXV infection. Our report describes a possible clinical feature of Mpox disease and illustrates the challenge of a disease that seems to present itself in different ways.