The Centers for Disease Control and Prevention (CDC) issued a dear colleague letter on July 27, 2022, describing important clinical manifestations and treatment considerations of monkeypox. The letter highlights that many persons with monkeypox are presenting with oral, genital, and anal mucosal lesions that may not be overtly visible on the exam. These lesions can be associated with significant pain which can have a profound impact on activities of daily living and often requires intervention.