The order Rodentia and in particular the Muridae are characterised by extremely high rates of chromosome evolution and remarkable chromosome diversity. The Praomys group (Murinae, Muridae and Rodentia) constitutes a diverse and abundant group divided into two complexes, the jacksoni complex and the tullbergi complex which includes the species Praomys tullbergi. Comparative chromosome painting using the two index genomes, Mus musculus and Rattus norvegicus, was performed resulting in a high resolution chromosome map for P. tullbergi. The combined use of rat and mouse probes and the assistance of the assembly of all the available sequencing data from Ensembl genome browser allowed a great dissection of P. tullbergi genome, the detection of inversion events and ultimately the refinement of P. tullbergi comparative map. A key achievement was the reconstruction of a high precision Muroidea ancestral karyotype (Muridae/Cricetidae and Murine) based in a broad species analysis combining previous reported comparative maps together with the presented data. This permitted the reconstruction of the evolutionary history of chromosome changes since the ancestral Muroidea genome and enlightened the phylogenetic relationships with the related species mouse and rat. The analysis of constitutive heterochromatin and its co-localisation with the identified evolutionary breakpoints regions was performed suggesting the involvement of repetitive sequences in the chromosome rearrangements that originated the present P. tullbergi genome architecture.