The 2022 mpox outbreak has rapidly emerged onto the global medical scene while the world continues to grapple with the COVID-19 pandemic. Unlike COVID-19, however, most patients with mpox present with skin findings, the evolving clinical presentation of which may be mistaken for other common skin diseases, particularly sexually transmitted infections. This Special Communication provides an overview of the evolution of mpox skin findings from its initial description in humans in 1970 to the present-day multinational outbreak.