The end of the Last Glacial Maximum (LGM) in Europe (~16.5 ka ago) set in motion major changes in human culture and population structure 1 . In Southern Europe, Early Epigravettian material culture was replaced by Late Epigravettian art and technology about 18-17 ka ago at the beginning of southern Alpine deglaciation, although available genetic evidence from individuals who lived ~14 ka ago 2–5 opened up questions on the impact of migrations on this cultural transition only after that date. Here we generate new genomic data from a human mandible uncovered at the Late Epigravettian site of Riparo Tagliente (Veneto, Italy), that we directly dated to 16,980-16,510 cal BP (2σ). This individual, affected by a low-prevalence dental pathology named focal osseous dysplasia, attests that the very emergence of Late Epigravettian material culture in Italy was already associated with migration and genetic replacement of the Gravettian-related ancestry. In doing so, we push back by at least 3,000 years the date of the diffusion in Southern Europe of a genetic component linked to Balkan/Anatolian refugia, previously believed to have spread during the later Bølling/Allerød warming event (~14 ka ago 4,6 ). Our results suggest that demic diffusion from a genetically diverse population may have substantially contributed to cultural changes in LGM and post-LGM Southern Europe, independently from abrupt shifts to warmer and more favourable conditions.