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Since the beginning of the Holocene, the Anatolian region has been a crossroads for populations and civilizations from Europe, Asia, and the Near to Middle East, with increasing interactions since the Bronze Age. In this context, we examine cranial discrete traits from a Byzantine population from southwest Turkey, excavated at the archeological site of Sagalassos; the site displays human occupation since the 12th millennium b.p. To investigate the biological history of this population, we analyzed the frequency distribution of 17 cranial discrete traits from Sagalassos and 27 Eurasian and African populations. Ward’s clustering procedure and multidimensional scaling analyses of the standardized mean measure of divergence (MMDst), based on trait frequencies, were used to represent the biological affinity between populations. Our results, considered within a large interpretive framework that takes into account the idea that populations are dynamic entities affected by various influences through time and space, revealed different strata of the Sagalassos biological history. Indeed, beyond an expected biological affinity of the Sagalassos population with eastern Mediterranean populations, we also detected affinities with sub-Saharan and northern and central European populations. We hypothesize that these affinity patterns in the Sagalassos biological package are the traces of the major migratory events that affected southwest Anatolia over the last millennia, as suggested from biological, archeological, and historical data.