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This article explores the plurality of referents associated with the term “dragon's blood” (“sanguis draconis”), a legendary substance that brings together Greco-Roman and Arabic medical knowledge, local vernacular traditions and artisanal practices, and new Spanish and Portuguese botanical discoveries. The study of dragon's blood reveals the interface between overlapping epistemic paradigms governing the definition, use, and circulation of complex material substances in early modern Europe, ranging from humanist learned discussions and artisanal experimentation to vernacular narratives of discovery, along with the shifting criteria of truth, authenticity, and value advocated by different communities of learning and practice.