In the present study, we investigate patterns of variation in the KIR cluster in a large and well-characterized sample of worldwide human populations in the Human Genome Diversity Project-Centre d'Etude du Polymorphisme Humain (HGDP-CEPH) panel in order to better understand the patterns of diversity in the region. Comparison of KIR data with that from other genomic regions allows control for strictly demographic factors; over 500,000 additional genomic markers have been typed in this panel by other investigators and the data made publicly available. Presence/absence frequencies and haplotypic associations for the KIR region are analyzed in the 52 populations comprising the panel and in accordance with major world regions (Africa, Middle East, Central Asia, East Asia, Europe, Americas, and Oceania). These data represent the first overview of KIR population genetics in the well-documented HGDP-CEPH panel and suggest different evolutionary histories and recent selection in the KIR gene cluster.