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This article aims to study the epistemological stakes which, during the Renaissance, built upon the fragmented and worldwide representations of syphilis and its various remedies. Confronting Spanish historiographer Oviedo and Portuguese physician Orta, who both took an interest in local syphilis treatments, may help to identify the operating modes underlying the legitimation of indigenous forms of knowledge. From guaiac wood described by Oviedo at Hispaniola to Chinese plants roots praised by Orta at Goa, new remedies were introduced to treat an epidemic described as being both of foreign origin and universal impact. What literary techniques, what scientific fantasies, what legitimation strategies could allow to assert the power of such indigenous forms of knowledge?