There are four theories about the origin of syphilis, of which the mostly represented one is the Columbian theory. This theory suggests that syphilis was brought into Europe in 1493 ad by the ship from Caribbean islands. The aim of this study is to test all theories on a sample of 403 skeletons: 135 from prehistory, 134 from antique, and 134 from medieval period and new age from the Dalmatia (Croatia). All skeletons were examined using standard anthropological methods. Paleopathological analysis was performed on each skeleton as well as additional radiographic method on one isolated skeleton. Paleopathological changes on skeletal remains connected with treponematosis. Paleopathological analysis revealed one skeleton from the antique period (second to 6th century ad) that exhibited skeletal markers similar to those described in one clinical case in which congenital syphilis was confirmed by a Wasserman reaction. Skeletal remains of this person were examined macroscopically and radiographically, and the differential diagnostics eliminated other considered pathologies as well as trauma. The finding of skeletal markers of syphilis on a skeleton from the antique supports the theory of pre‐Columbian syphilis origin. Anteric I, Basic Z, Vilovic K, Kolic K, and Andjelinovic S. Which theory for the origin of syphilis is true? J Sex Med 2014;11:3112–3118.