The genus Ctenomys present a wide 2n and fundamental number (FN) variation in Uruguay and throughout their distribution across the south of the Neotropical region. In this study we analyze chromosome variation of this genus in Uruguay using G and C bands. G-band comparison makes clear that this chromosome variation is reduced if we take into account entire chromosomes and chromosome arms homologies. This could be explained as an adaptation to chromosome variation (2n and FN) without changing gene order or linkage groups. On the other hand, C-banding showed a high variability in amount and localization in the karyotypes analyzed here. These differences could be due to differential amplification of the repetitive DNA (RPSC) characteristic of this genus. Nevertheless, other mechanisms could be involved as repetitive DNA interchange at the chromocenters in the meiosis pachytene, where non homologous chromosomes meet. In this scenario, chromosome rearrangements such as Robertsonian translocations and whole chromosome conservation are of particular interest since these provide a way to conserve gene order. Why Ctenomys chromosomes are prone to rearrangements is not clear, albeit several mammal species present a similar picture. This kind of chromosome change could be involved in the maintenance of chromosome order at the nuclear level. In this paper, we present evidence showing that chromosome and genetic changes are not unavoidably related in Ctenomys, which questions the hypothesis about speciation based on chromosomal changes.