Syphilis can show unexpected clinical characteristics rendering its diagnosis difficult. We report on two cases of secondary syphilis presenting with atypical histories of knee or cervical pain and cough. Both had bone involvement and one, pulmonary involvement, documented by MRI, CT scan and PCR. Both responded well to therapy with intravenous aqueous penicillin G followed by intramuscular benzathine penicillin G, but a pulmonary adenocarcinoma was diagnosed during follow-up in one case.