Comparative genomic in situ hybridization (CGH) studies have marked regions of unbalanced genomic alterations in a variety of human solid and hematological malignancies. Subsequent molecular analysis helped to pinpoint genes contributing to tumorigenic development and progression. CGH has since become a routine tool in molecular diagnostics and cancer research. Since mice and rats represent major model systems for human malignancies, CGH was soon adapted for tracing DNA copy number changes in experimental rodent tumor genomes. A stronghold of this approach is the potential transfer of information to the human situation by use of comparative maps of mouse and rat, and the human genome. This allows for an evaluation and validation of rodent tumor models at the genomic level. This review will illuminate the insights obtained by CGH analysis of rodent tumor genomes and the comparative transfer of this information between rodents and human.