In situ hybridization or hybridohistochemistry has evolved in recent years in a new histologic modality. In situ hybridization (ISH) can be used for the detection of DNA (DISH) or RNA (RISH). The potential diagnostic value within a pathologic setting are well recognized. In this review paper, we summarize the use of DISH in a pathologic setting for the detection of chromosomal aberrations and localization of DNA-viruses like cytomegalovirus and Epstein Barr virus. RISH which is still in a more experimental stage can be applied for the localization of RNA-virus, like human immunodeficiency virus. However, the most important application of RISH will be the detection of gene-expression at the level of mRNA. Potentially this has many applications especially in early diagnostics of neoplastic tissues. Finally, we have summarized some pitfalls which may hamper the introduction of in situ hybridization for diagnostic purposes and some future developments in ISH.