The origin of human chromosomes (HSA) 7, 16, and 19 was studied by comparing data obtained from chromosome banding, chromosome painting, and gene mapping in species belonging to 11 orders of placental mammals (Eutherians). This allowed us to propose the reconstruction of their presumed ancestral forms. The HSA7 homologs were composed of two parts, the largest forming an acrocentric. The smallest formed one arm of a small submetacentric; the other arm was composed of sequences homologous to the short arm of HSA16 (HSA16p). The sequences homologous to the long arm of HSA16 (HSA16q) were associated with sequences homologous to the long arm of HSA19 (HSA19q) and formed another submetacentric. From their origin, these chromosomes underwent the following rearrangements to give rise to current human chromosomes: centromeric fission of the two submetacentrics in ancestors of all primates (∼80 million years ago); fusion of the HSA19p and HSA19q sequences, originating the current HSA19, in ancestors of all simians (∼55 million years ago); fusions of the HSA16p and HSA16q sequences, originating the current HSA16 and the two components of HSA7 before the separation of Cercopithecoids and Hominoids (∼35 million years ago); and finally, pericentric and paracentric inversions of the homologs to HSA7 after the divergence of orangutan and gorilla, respectively. Thus, compared with HSA16 and HSA19, HSA7 is a fairly recent chromosome shared by man and chimpanzee only.