The composition of cutaneous lesions from 158 patients with confirmed cutaneous T cell lymphoma, 91 patients with suspected cutaneous T cell lymphoma, and 145 patients with lymphoid disorders other than cutaneous T cell lymphoma was quantitated in situ with the use of commercially available murine monoclonal antibodies that identify the Pan T, T-helper/inducer (T_h), T cytotoxic/suppressor (T_s), and Pan B lymphocyte subsets. On average, cutaneous infiltrates of confirmed cutaneous T cell lymphoma were found to contain significantly more T_h and less T_s or Pan B cells compared to benign lymphoid disorders. Moreover, when analyzed in terms of the type of lesion examined by biopsy, the absolute amount of T_h cells progressively expands with increasing magnitudes of infiltrate in the dermis while the amount of Ts and Pan B cells remains relatively constant among lesions. A useful diagnostic criterion (anti-Leu ¼ ≥70% and anti-Leu 3a/anti-Leu 2a ratio ≥6) correctly discriminated between cutaneous T cell lymphoma and non-cutaneous T cell lymphoma in 87.5% of cases. A positive immunodiagnostic result also may be useful for the prediction of subsequent histopathologic confirmation of cutaneous T cell lymphoma in patients who have suspect lymphoid infiltrates, such as alopecia mucinosis or idiopathic generalized erythroderma, when first seen. With the use of multivariate analysis, stage and possibly the percentage of T_h cells within the T cell component in cutaneous infiltrates were covariates with significant relationships to survival in patients with confirmed cutaneous T cell lymphoma. In addition, T_s cells in infiltrates did not correlate significantly with observed responses to topical treatment and subsequent course in pretumorous mycosis fungoides. These results indicate that Ts cells play little biologic role in modifying the natural history of cutaneous T cell lymphoma.