The hypothesis of an American origin of acquired (venereal) syphilis and other infectious diseases carried by Columbus's crew has been considered for a long time as the most plausible one, and has been supported recently by considerable anthropological and molecular evidence. According to this line of thought, it can be argued that Spain would have been the gateway of acquired syphilis, which quickly expanded after the return of Columbus in the late 15th century. However, the hypothesis that syphilis previously existed in Europe but went unrecognized has also been considered by many authors. The present work reports one Pre-Columbian putative case of venereal syphilis found in a Spanish necropolis and radiocarbon dated to the 9th-11th century. The complexities of carrying out accurate diagnoses in remains from archaeological timeframes are addressed by the combined use of palaeopathological, medical, and histological techniques. The results, which point toward third-stage acquired syphilis, spark discussion about the need to revisit or complement the theories and hypothesis on the origin of syphilis in the light of a growing body of cases from European historical populations.