Some 70 Ma, rodents arose along a branch of our own mammalian lineage. Today, about 40% of all mammalian species are rodents and are found in vast numbers on almost every continent. Not only is their proliferation extensive but also the rates of DNA evolution vary significantly among lineages, which has hindered attempts to reconstruct, especially the root of, their evolutionary history. The presence or absence of rare genomic changes, such as short interspersed elements (SINEs), are, however, independent of high molecular substitution rates and provide a powerful, virtually homoplasy-free source for solving such phylogenetic problems. We screened 12 Gb of rodent genomic information using whole-genome three-way alignments, multiple lineage-specific sequences, high-throughput polymerase chain reaction amplifications, and sequencing to reveal 65 phylogenetically informative SINE insertions dispersed over 23 rodent phylogenetic nodes. Eight SINEs and six indels provide significant support for an early association of the Mouse-related and Ctenohystrica (guinea pig and relatives) clades, the Squirrel-related clade being the sister group. This early speciation scenario was also evident in the genomewide distribution pattern of B1-related retroposons, as mouse and guinea pig genomes share six such retroposon subfamilies, containing hundreds of thousands of elements that are clearly absent in the ground squirrel genome. Interestingly, however, two SINE insertions and one diagnostic indel support an association of Ctenohystrica with the Squirrel-related clade. Lineage sorting or a more complex evolutionary scenario that includes an early divergence of the Squirrel-related ancestor and a subsequent hybridization of the latter and the Ctenohystrica lineage best explains such apparently contradictory insertions.