Here, we present analysis of data on comparative chromosome painting produced using various chromosome-specific libraries for members of different Glires groups. Based on the results of comparative cytogenetic and molecular studies, the modern rodents can be conventionally classified into two groups with sharply differing directions and tempoes of karyotypic evolution. One group (suborders Sciuromorpha, Castorimorpha, and Anomaluromoprpha) preserved conserved genomes, which are probably close in structure to the genome of the ancestor of all mammals. The genomes of the other group (suborder Myomorpha) underwent "catastrophic evolution," which resulted in numerous breaks and fusions of the ancient chromosomes. The current data do not allow unambiguously assigning the order Hystricomorpha to any of these groups.