This study demonstrates that the detection of rearrangement of the T-cell receptor gene and adult T cell leukemia virus or human T cell lymphotropic virus type I (ATLV/HTLV-I) integration in the genome are sensitive and practical methods for the diagnosis and characterization of cutaneous T cell neoplasms. Biopsy specimens obtained from small skin nodules containing a dense infiltration of lymphocytes were analyzed by Southern blotting with the use of probes for both the beta-chain of the T-cell receptor gene and the ATLV/HTLV-I genome. DNA samples from one patient with early, chronic adult T cell lymphoma or leukemia, revealed the monoclonal proliferation of lymphocytes. For another patient with early cutaneous T cell lymphoma analysis by Southern blotting with the beta-chain probe of DNA from three separate lesions revealed identical rearranged bands, indicating not only the monoclonal proliferation of T cells in each lesion but also the clonal origin of each lesion. In contrast, analysis by Southern blotting of DNA samples extracted from three nodules from a patient with lymphomatoid papulosis showed no rearranged band and therefore no clonal proliferation. DNA extracted from blood lymphocytes of these patients failed to hybridize with the probes described above as a rearranged band. These results indicate that analysis of DNA extracted from skin lesions may have diagnostic value in determining monoclonal proliferation of lymphocytes in patients with early stage cutaneous lymphomas.