The advantages and disadvantages of the immunofluorescence and immunoperoxidase techniques and an introductory description of the major variations of the basic immunoperoxidase method are discussed. The ability to identify intermediate filaments, T and B lymphocyte cell markers, S-100 proteins, myelin basic protein, and carcinoembryonic antigen in tissue sections can assist the dermatopathologist in classifying undifferentiated or histologically similar-appearing tumors. A systematic approach to the diagnosis of a majority of these tumors with the use of immunoenzyme staining is provided.