Chemokines are critical molecules in leukocyte trafficking, promoting site-specific migration to various tissues. The chemokine receptor CCR4 has recently been associated with skin-homing T cells. In view of the potential importance of CCR4 in skin homing of T cells, we investigated the expression pattern of CCR4 and its ligands TARC/CCL17 and MDC/CCL22 in the peripheral blood and skin of patients with cutaneous T cell lymphoma, a putative malignancy of the skin-homing T cells. In this study we analyzed the pattern of coexpression of the skin-homing molecules cutaneous lymphocyte antigen (CLA) and CCR4 in the blood and skin of patients with cutaneous T cell lymphoma. In the blood of cutaneous T cell lymphoma patients with peripheral blood involvement we found significantly increased percentages of T cells displaying the skin-homing phenotype (CLA+CCR4+) compared with healthy individuals. T cells expressing CLA and CCR4 were also found at high levels in cutaneous T cell lymphoma lesions along with abundant expression of the two CCR4 ligands TARC/CCL17 and MDC/CCL22. These data may explain, in part, why these T cells accumulate in the skin, a diagnostic feature of cutaneous T cell lymphomas.