We describe a patient with therapy-resistant cutaneous T-cell lymphoma, Sézary syndrome variant, in association with concurrent polyarthritis and vitiligo, who was successfully treated with extracorporeal photochemotherapy (ECP). The combination of Sézary syndrome with seronegative rheumatoid arthritis is rare. In our patient the T-cell lymphoma was refractory to standard treatments that included psoralen—UVA, lymph node irradiation, and polychemotherapy. ECP has been shown to be effective in the treatment of selected cases of Sézary syndrome. There is a strong suggestion that ECP as a monotherapy can provide a significant benefit for other T-cell-mediated diseases including rheumatoid arthritis. In spite of a disease duration of 10 years, a very low CD8 cell count (2% of lymphocytes), a very high CD4 cell count (94%), and multiple unsuccessful chemotherapeutic trials before initiation of ECP, our patient achieved a long-lasting complete remission of both diseases with normalization of the CD4⁺ and CD8⁺ T-lymphocyte subsets. Concurrent developing vitiligo was unaffected by ECP. (J Am Acad Dermatol 2003;48:220-6.)