The cases of monkeypox described in the current outbreak have some atypical features. The rash may start in the genital and perianal areas, the rash may not always disseminate to other parts of the body and typical prodromal symptoms may be mild or absent. These features of the newest monkeypox cases can easily be confused with sexually transmitted infections (STI). It is important to comprehensively evaluate patients presenting with genital or perianal ulcers for STIs. However, co-infections with monkeypox and STIs have been reported and the presence of an STI does not rule out monkeypox. Patients with a new characteristic rash or who meet one or more of the epidemiologic criteria and in which there is a high suspicion should be tested for monkeypox.