Based on the analysis of DNA from present-day and ancient individuals on the Isthmus of Panama, an interdisciplinary research team, led from the Universities of Pavia and Pablo de Olavide (Seville), explains complex pre-Hispanic burials excavated in Panama City and highlights the genomic distinctiveness of the Isthmo-Colombian area. The research has also revealed a previously undescribed ancestry among ancient Indigenous peoples of the Americas, unique to the region and detectable in the ancient pre-Hispanic individuals as well among the self-identified descendants of current Indigenous, African and Hispano-Indigenous groups.