During the last decade, pathology has progressed remarkably with the incorporation of molecular techniques into the arena of diagnostics. Fluorescence in situ hybridization (FISH) is a molecular histopathological technique that can be readily used to identify DNA or RNA abnormalities at the cellular level with the use of an epifluorescence microscope. FISH technology is applicable to most forms of tissue preparation including peripheral blood, bone marrow, solid tumors, body fluids, amniotic fluids and products of conception. This technology enables the identification of gene, chromosomal and genomic abnormalities in histologically processed material, exfoliated cells, smears and monolayer cultures with appropriate fluorescently labeled DNA probes. The following chapter provides a broad overview and extensive technical details of FISH technology, thereby providing the reader with a complete picture of the field. In light of the applicability of this technology to interphase cells, FISH can serve to provide the pathologist with a genotypic analysis to accompany the phenotypic morphology of the cells for the purpose of diagnosis and prognosis. The utility of such a correlation defines FISH technology as a revolutionary technique in the field of research and diagnostics, particularly in areas of cancer, genetic abnormalities and infectious diseases.