Karyotypic fission theory of Todd offers an explanation for the diverse range of diploid numbers of many mammalian taxa. Theoretically, a full complement of acrocentric chromosomes can be introduced into a population by chromosomal fission. Subsequent inheritance of ancestral chromosomes and paired fission derivatives potentially generates a diploid range from the ancestral condition to double its number of chromosomes. Although it is undisputed that both chromosomal fission and fusion ("Robertsonian rearrangements") have significantly contributed to karyological diversity, it is generally assumed that independent events, the fission of single chromosomes or the fusion of two chromosomes, are the sources of such change. The karyotypic fission idea by contrast posits that all mediocentric chromosomes simultaneously fission. Here I propose a specific cell biological mechanism for Todd's karyotypic fission concept, "kinetochore reproduction theory," where a complete set of dicentric chromatids is synthesized during gametogenesis, and kinetochore protein dephosphorylation regulates dicentric chromatid segregation. Three postulates of kinetochore reproduction theory are: (i) breakage of dicentric chromosomes between centromere pairs forms acrocentric derivatives, (ii) de novo capping of newly synthesized acrocentric ends with telomeric DNA stabilizes these derivatives, and (iii) mitotic checkpoints regulate chromosomal disjunction to generate fissioned karyotypes. Subsequent chromosomal rearrangement, especially pericentric inversion, increases the probability of genetic isolation amongst incipient sympatric species polytypic for fission-generated acrocentric autosomes. This mechanism obviates the requirement for numerous independent Robertsonian rearrangements and neatly accounts for mammalian karyotype evolution as exemplified in analyses of Carnivora, Artiodactyla, and Primates.