Bone involvement of syphilis can be observed in tertiary and congenital syphilis. It is infrequent during the secondary stage. The skull is the most affected bone in secondary syphilis, and its most frequent form of presentation is proliferative osteitis. If the skull is affected, headache is usual and can be as intense as in meningitis. Osteolyitic lesions may be seen in complimentary imaging studies, with a moth eaten aspect. These lesions raise concern over a number of differential diagnoses, among which are infectious, inflammatory and neoplastic diseases. The definitive diagnosis is made by bone biopsy of the compromised bone. Molecular techniques in the affected tissues increases diagnostic performance. There is no standardized treatment protocol for syphilis since there are no guidelines available. We report a case of a 19 year old female, presenting with a unique osteolytic lesion in the skull due to secondary syphilis.