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In this paper i will discuss competing historical demographic/political narratives in the framing and interpretation of human population genetic and genomic data in Mexico (1960–2025). Drawing on the changing published and widely circulated “common-sense” views of Mexican geneticists regarding historical mestizaje (racial admixture) and human population genetic admixture between ca. 1960 and 2025, as well as on the evolving cultural and political debates around the meanings of mestizaje, I will analyze the trajectory of successive Mexican anthropological and medical population genetics/genomics projects. I focus on how twentieth-century post-revolutionary nationalist narratives—centered on Mestizo unity and mixture—eventually came to share the stage with more nuanced multiculturalist (even decolonial) perspectives emphasizing pre-Hispanic Indigenous genomic substrates (often conceptualized as isolates). I will show how these shifts produced a dialectical movement between the framing of research projects and the interpretation of their results. The ambivalences and conceptual obscurities generated by the oscillation between these two poles will be discussed.