International audience Human tuberculosis has been considered for a long time as a model of animal infection transmitted to humans, resultingfrom cattle domestication at the Neolithic period. A decade ago, studies of molecular phylogeny of the Mycobacterium tuberculosiscomplex (MTBC) has challenged this dogma, suggesting that this human infection could be as old as the human species and emergedca 2-3 Myrs ago. Yet, recent studies of molecular clock computations proposed that human tuberculosis could not be older than6 kyrs BP. In order to bring new data to this debate, we studied the paleopathological evidence of tuberculosis on a large sample of twoNeolithic sites from Syria in the Near East, cradle of agriculture and domestication: Dja’de el-Mughara (9310-8290 cal. BC) locatedin the Middle Euphrates Valley (Northern Syria) and Tell Aswad (8200-7500 cal. BC) in the Central Levant (Southern Syria). Bothsites have delivered skeletal remains of more than one hundred individuals deriving from different funeral contexts. We used methodsof paleopathology, microstructural analysis (μ-CT) and paleomicrobiology. The paleopathological study gave evidence to the mostancient paleopathological known cases of human TB (one adult and nine immature individuals at Dja’de el-Mughara and one adultat Tell Aswad) predating or accompanying the emergence of animal domestication. Among the eleven cases identified, five individualsfrom Dja’de el-Mughara have been buried in the House of the Dead, while the other individuals at both sites were found in primary,plural and mixed burials. On the basis of these results, the future challenge would be to understand the close contact between humansand animals role in the evolution of MTBC and the mechanisms of modern human tuberculosis strains emergence and spread. For thisreason, the Levant is a crucial region as a key center for domestication and sedentism origins.