The measurement of aneuploidy rates in mammalian cells can be slow and laborious. This problem has been alleviated in budding and fission yeasts by the development of colour-based mini-chromosome assays. This allows for millions of cells to be easily examined for mini-chromosome loss or non-disjunction by changes in colour sectoring in colonies on agar plates. We have applied a similar strategy by using gene-targeting to insert either green or red fluorescent reporter genes into the non-essential mouse Y chromosome. Transgenic mice have been generated with this reporter Y chromosome, which are healthy and fertile. In this study we show that we can detect fluorescent protein expression in multiple tissues in the adult male, as well as in the whole male embryo. To test the utility of the reporter mouse strains in measuring chromosome loss, we have crossed the mice to chromosome instability mutants. Male mid-gestation embryos from these instability mutant crosses show less fluorescent protein expression when compared to the reporter Y chromosome on the wild-type background. These mouse reporter strains may be useful in the screening of genetic and environmental factors that contribute to aneuploidy.