The authors report an atypical case of secondary syphilis in an adolescent female presenting to a tertiary-care center with fever, weight loss, oral sores, painful inguinal lymphadenopathy, and transient macular rash. Given the lower prevalence of syphilis in adolescent females, this infection was not included on the initial differential diagnosis. The evolving presentation of syphilis over time complicates the diagnosis and management of these infections, as it did for the patient in this report. The authors provide a detailed discussion of the patient's clinical findings, including the protean features of syphilis infection. This case is particularly relevant to the fields of general pediatrics and pediatric hospital medicine.