On December 7, CDC issued a health advisory to notify clinicians and health departments about the occurrence, geographic spread, and sexually associated human-to-human transmission of Clade I Monkeypox Virus (MPXV) in the Democratic Republic of the Congo (DRC). MPXV has two distinct genetic clades (subtypes), and cases of Clade I MPXV have not been reported in the United States at this time. A clade is a broad grouping of viruses that has evolved over decades and is a genetic and clinically distinct group. However, clinicians should be aware of the possibility of Clade I MPXV in travelers who have been in DRC. Clinicians should notify their state health department if they have a patient with mpox-like symptoms, which may include a diffuse rash and lymphadenopathy, and recent travel to DRC. Clinicians should also submit lesion specimens for clade-specific testing for these patients.