The origins of syphilis are not known, though it does not appear to have been known in Europe in Classical times. One school of thought has it that syphilis was brought back to Europe from the New World by the crew of Christopher Columbus's first voyage. The evidence is circumstantial, and based on the fact that the first recognized outbreak was at Naples in 1494 where a number of Spaniards from the Columbus crew participated in the army of Charles VIII of France. By 1498 the Portuguese explorers had lovingly introduced the disease to India.

Because of the outbreak in the French army, it was first called morbus gallicus, or the French disease. In that time it is noteworthy that the Italians also called it the "Spanish disase", the French called it the "Italian" or "Neapolitan disease", the Russians called it the "Polish disease", and the Arabs called it the "Disease of the Christians". The name "syphilis" was first applied by Girolamo Fracastro in 1530 from the name of a shepherd in a poem by Leonardo da Vinci.