In the past decades, prehistoric hunter-gatherers of the Cis-Baikal region has been a subject of multidisciplinary research. In this study, we used nonmetric cranial traits to assess the genetic relationships between various spatial and temporal groups of Cis-Baikal Middle Holocene hunter-gatherers and to reveal genetic continuity between the Cis-Baikal Neolithic-Bronze Age population and modern native Siberians. Cranial series belonging to the bearers of the Early Neolithic Kitoi (n = 72), Late Neolithic Serovo (n = 54), and Early Bronze Glazkovo (n = 98) cultures were examined. Phenotypic differentiation was analyzed by the mean measure of divergence and Nei's genetic distances. Our results revealed several patterns of spatiotemporal biodiversity among the Cis-Baikal Middle Holocene populations, including biological similarity between the Early and Late Neolithic-Bronze Age groups, which suggests that the temporal hiatus between the Early and Late Neolithic does not necessarily imply genetic discontinuity in the region. The following possible scenarios of population history in the Cis-Baikal region are proposed: 1) continuous occupation with outside invasion of new migrant groups in the Late Neolithic and Bronze Age and 2) migration of the Early Neolithic groups to the nearby regions and subsequent return of their descendants to the ancestral territory. A comparison of Cis-Baikal Neolithic populations with modern Siberian natives suggests that the Сis-Baikal region could have been a source area for population expansions into different parts of Siberia in the Neolithic and Bronze Age times. Am J Phys Anthropol 155:559–570, 2014. © 2014 Wiley Periodicals, Inc.