Recent advances in protocols for multicolor fluorescence in situ hybridization (FISH) mark a major milestone in the field of molecular cytogenetics. Brilliant chromosome images have been presented, where each chromosome homolog is depicted in a different color. The easy recognition of chromosomes seems to simplify karyotype analysis considerably and the procedure is meant to open new avenues for scanning human and other genomes for chromosomal rearrangements. How will this development change the field of cytogenetics? In this review the current applications that benefit from the new protocols are summarized and future perspectives are discussed.