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Molecular phylogeny work has shown that tuberculosis is ancient human-adapted infection predating the Neolithic period. They also show that the Upper Paleolithic is a key period of emergence of the MTB complex strains, contemporary with the exit of modern man from Africa. Despite the richness of Upper Paleolithic sites in Eurasia and the relative abundance of human remains, the only proven case of Paleolithic tuberculosis has been described so far date from the Azilian, a culture of the European Final Paleolithic, which is more recent than the ancient Neolithic sites of the Near East, area that currently hold the record for the oldest paleopathological evidence of tuberculosis. The purpose of this review is to present evidence for the existence of tuberculosis in the Paleolithic and to list hypotheses explaining the weak demonstrative contribution of paleopathology for pre-Neolithic periods., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Ltd.)