The intermediate filaments represent an important group of differentiation markers that have proven to be useful for the diagnosis and classification of human neoplasms. The immunohistochemical demonstration of these proteins is subject to numerous technical variables that include specificities and patterns of reactivities of polyclonal antisera and monoclonal antibodies, cross-reactivities of "specific" monoclonal antibodies with other intermediate filaments and other classes of antigens, masking of certain epitopes due to physiologic or pathologic changes in cells, effects of tissue fixation and subsequent tissue processing, and the sensitivity of the particular immunohistochemical detection system employed. Moreover, a wide variety of microenvironmental signals may affect the patterns of expression of intermediate filament proteins in different pathological conditions. For accurate interpretation of intermediate filament immunoreactivity, the pathologist must be familiar with the various sources of error relating to false positive or negative results. This requires the availability of optimally fixed tissues, a well-characterized set of antibodies to intermediate filament antigens and access to the results of extensive performance testing.