A method for painting a chromosome or chromosome region by fluorescence in situ hybridization (FISH) without blocking DNA is described. Both unique sequence and repetitive sequence components of a fluorescently labeled probe are hybridized under low-stringency conditions, but the chromosomes are washed in such a manner that repetitive sequences are differentially removed, while region-specific unique sequence fragments remain bound to the target chromosomes. We refer to this differential retention and removal of probe components as differential stability FISH.