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Before the end of the Last Glacial Maximum (LGM, ∼16.5 ka ago) set in motion major shifts in human culture and population structure, a consistent change in lithic technology, material culture, settlement pattern, and adaptive strategies is recorded in Southern Europe at ∼18–17 ka ago. In this time frame, the landscape of Northeastern Italy changed considerably, and the retreat of glaciers allowed hunter-gatherers to gradually recolonize the Alps. Change within this renewed cultural frame (i.e., during the Late Epigravettian phase) is currently associated with migrations favored by warmer climate linked to the Bølling-Allerød onset (14.7 ka ago), which replaced earlier genetic lineages with ancestry found in an individual who lived ∼14 ka ago at Riparo Villabruna, Italy, and shared among different contexts (Villabruna Cluster). Nevertheless, these dynamics and their chronology are still far from being disentangled due to fragmentary evidence for long-distance interactions across Europe. Here, we generate new genomic data from a human mandible uncovered at Riparo Tagliente (Veneto, Italy), which we directly dated to 16,980–16,510 cal BP (2σ). This individual, affected by focal osseous dysplasia, is genetically affine to the Villabruna Cluster. Our results therefore backdate by at least 3 ka the diffusion in Southern Europe of a genetic component linked to Balkan/Anatolian refugia, previously believed to have spread during the later Bølling/Allerød event. In light of the new genetic evidence, this population replacement chronologically coincides with the very emergence of major cultural transitions in Southern and Western Europe., The research was supported by the European Union through the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement no. 724046 – Success awarded to S.B., http://www.erc-success.eu; grant agreement no. 803147 Resolution awarded to S.T., https://site.unibo.it/resolution-erc/en) as well as through the European Regional Development Fund (project no. 2014–2020.4.01.16–0030 to C.L.S. and T.S.) and projects no. 2014-2020.4.01.16-0024 and MOBTT53 (L.P.), by the Estonian Research Council personal research grant (PRG243; C.L.S.), and by UniPd PRID 2019 (L.P.).