Oecomys is a taxonomically complex and cytogenetically diverse genus with a controversial intraspecific phylogenetic relationship. Karyotypic analyses, using whole chromosome probes from Hylaeamys megacephalus (HME, Sigmodontinae, Oryzomyini) in some taxonomic lineages of this genus have been detecting the rearrangements that shaped their karyotypes, in addition to revealing relevant insights into the taxonomic status of these taxa. Thus, intending to investigate the chromosomal evolution of the genus, we characterized the karyotype of Oecomys rutilus (ORU) with HME probes, establishing chromosomal homology maps with the karyotypes of other congeners that already mapped with the same set of probes. The chromosomal phylogeny obtained by Maximum Parsimony analysis recovered the genus Oecomys as monophyletic, with moderate bootstrap support (68%). This clade branches into two large groups, the first including O. rutilus followed by O. catherinae - Rio de Janeiro and O. catherinae – Pará; the other group includes O. auyantepui followed by O. paricola cytotype C and O. paricola cytotype A + cytotype B. We detected that these taxa underwent intensive reorganization in their karyotypes, and the rearrangements that produced this diversity were 15 pericentric inversions, 12 centric fusions, 11 fissions, 5 in tandem fusions, 8 simple translocations, 1 neo-centromere and addition/deletion of constitutive heterochromatin on two autosomes and the X chromosomes. However, despite the high number of chromosomal rearrangements found, we identified some entirely conserved syntenic blocks shared among all species analyzed. From these data, we hypothesized a putative ancestral karyotype (2n=60/FN= 62) for the species analyzed. We also detected exclusive characteristics for ORU, the syntenic blocks HME 1/20/4, HME (16,17)/3, HME 2/1, HME 2/7, HME 5/(9,10)/8, HME 19/12. Here we provide an overview of the chromosomal reorganization of the genus that points to a high chromosomal diversity, and demonstrates that chromosomal rearrangements play a significant role in the radiation of these species.