DNA hybridization techniques are now commonly used in studies of endocrine disease. Although solution and filter hybridization have been more widely used in endocrine studies, ISH offers many advantages to the pathologist. Individual cells can be visualized directly with the microscope to study the expression of specific gene products. ISH is somewhat similar to immunohistochemistry and can be set up rapidly in most histology laboratories, especially when nonradioactive biotinylated probes are used. The ability to combine ISH with immunochemical techniques offers to the pathologist the use of two powerful diagnostic tools simultaneously. Although DNA hybridization has only begun to have an impact in diagnostic pathology, many studies using this technique in the diagnosis of endocrine diseases are emerging. The availability of more probes, especially with nonradioactive detection systems, should accelerate the application of these techniques in diagnostic pathology. As the number of molecular probes available for hybridization studies increases, pathologists can have a major impact in this field by carefully evaluating probes that have potential diagnostic value for their specificity and sensitivity in a wide variety of normal and abnormal human tissues. Such careful and critical analyses will contribute greatly to the confidence with which these molecular probes can be used as another tool in the analysis of difficult diagnostic lesions. Molecular hybridization techniques will also contribute greatly to our knowledge of basic biology and pathophysiology in the study of abnormal gene expression in endocrine and other pathologic conditions.