The diagnosis of syphilis remains challenging. The absence of classical features of the disease, such as the rash of secondary syphilis or genital lesion, may pose diagnostic difficulties. In this article, we report a case of secondary syphilis in which the clinical syndrome and pattern of fluorodeoxyglucose uptake mimicked malignant lymphoma. This case highlights the importance of thorough history taking including sexual contact. Clinicians should be alert for syphilis-underlying unexplained lymphadenopathy, even in the absence of typical rash or genital lesion.