Our combined ultrastructural, immunohistochemical, histologic, and clinical studies over the past five years have allowed us to compile diagnostic criteria useful in the evaluation of cutaneous lymphomas. As a group, mycosis fungoides (MF) patients could be distinguished from those with benign disorders of skin using ultrastructural morphometry (mean form factor and perimeter values), but with some overlap between groups. Another approach, the ultrastructural histogram method, however, clearly separated MF patients from patients with chronic dermatitis. Immunohistochemistry was useful in distinguishing cases of cutaneous peripheral T-cell lymphoma from MF cases on the basis of the occurrence of "novel phenotypes." Neoplastic T-cell infiltrates of skin can usually be distinguished from benign polyclonal T-cell infiltrates by the presence of one T-cell subset to the exclusion of others. Patients with convoluted B-cell lymphomas could also be distinguished from MF patients using ultrastructural morphometric dual parameter analysis. The diagnostic complexity of several cutaneous T-cell lymphoma cases is illustrated. We have emphasized in this study the strength of combining quantitative electron microscopy, immunohistochemistry, and histology in the diagnostic workup of cutaneous lymphomas. This integrative approach may be necessary to assure a definitive diagnosis in difficult cases.