Previous studies have demonstrated that quantitative analysis of nuclear convolution of lymphoid cells in electron micrographs is a valuable method of differentiation between well-established cutaneous T-cell lymphoma (CTCL) and chronic benign skin disease. The usefulness of these methods in the diagnosis of early and controversial cases of CTCL has, however, not been fully established. In the present study the authors compared the diagnostic accuracy of two different quantitative ultrastructural methods on a group of 77 patients suspected of having early CTCL. These methods included measurements of the nuclear contour index (NCI) as well as a simple counting of the number of sharply angled nuclear indentations of at least 75 lymphoid cells present on electron micrographs. The results were correlated with the final diagnosis after a follow-up period of 1 to more than 10 years. Measurement of the NCI proved to be a much more sensitive method than determination of the percentage of cells having no sharply angled nuclear indentations (sensitivity, 96% and 62%, respectively). None of these two methods produced false-positive diagnoses. It is concluded that quantitative ultrastructural methods, in particular, NCI measurements, are an important adjunct in the diagnosis of CTCL, even in early and controversial cases.