Cutaneous T-cell lymphomas (CTCLs) are known to show monoclonal T-cell infiltrates late in the course of the disease. However, detection of monoclonal T-cell proliferation in early stages is difficult. To investigate the possibility that clones might appear only as minor subpopulations, we analyzed the proliferative activity of T cells expression certain variable (V) regions of the T-cell receptor (TCR). In biopsy specimens from 27 patients with CTCLs, all T cells expressing the V regions V alpha 2, V beta 5a, V beta 5b, V beta 6, V beta 8 and V beta 12 accounted for less than 5% of the total infiltrate. In the vast majority of the cases, less than 3% of the cells expression one TCR V region proliferated. In one case of mycosis fungoides, however, an epidermotropic clone expressing V beta 8 was detected. This clone was present in two distinct lesions from different anatomic sites and was found in an early relapse 1 year after complete remission following PUVA therapy. The case described here documents the possibility of clonal disease early in the course of mycosis fungoides.