Fluorescent in situ hybridization (FISH) is a molecular cytogenetic technique that exploits the availability of recombinant deoxyribonucleic acid (DNA) technology. In metaphase FISH, a specific nucleic acid sequence (probe) is bound to the homologous segment on a metaphase chromosome in a fixed preparation on a glass slide. The presence of a region-specific DNA sequence in a nondividing cell can be detected using interphase FISH. Interphase cytogenetics via FISH can be performed on fixed cells harvested during a routine culture, on tissue sections and on many cytologic specimens. Specific examples of clinical and research applications are discussed to illustrate the utility of FISH in the detection of constitutional and acquired chromosomal abnormalities.