A 66-year-old woman presented with 9 days of left clavicle pain, with no history of recent trauma. CT images showed a left clavicle fracture with a surrounding soft tissue mass. An 18F-FDG PET/CT scan revealed increased FDG uptake in the tonsils, multiple lymph nodes, and the pathologically fractured clavicle, initially suggesting malignancy. However, serologic tests and pathology confirmed syphilitic lymphadenitis and osteomyelitis. Given the inguinal and cervical lymphadenopathy with FDG uptake, potential bone destruction, or pathological fractures mimicking malignancy, syphilis should be considered in the differential diagnosis. Serologic testing and Treponema pallidum screening are essential.