Author summary Human monkeypox is the most significant Orthopoxvirus infection since the eradication of smallpox. The disease is endemic in Africa and the majority of cases occur in the Congo Basin. Correct identification of patients is critical to deployment of efficient control measures to prevent further transmission and appropriate care for the patient. An evaluation of two surveillance case definitions revealed that the definitions had high sensitivities but low specificities for correct case identification, which results in the identification of patients with other rash illnesses. Several signs and symptoms of laboratory-confirmed monkeypox cases were identified that could be used to aid in the development of surveillance case definitions to correctly identify cases. Laboratory diagnostics continue to be an important part of correct patient identification in order to control the disease and provide adequate care.