Background. Therapeutic biologic agents are uncommonly associated with lymphoma. Case presentation. We report a patient with psoriasis treated with the biologic agents efalizumab (Raptiva®) and etanercept (Enbrel®), who developed painless lymphadenopathy with peripheral lymphocytosis during treatment, simulating a non-Hodgkin lymphoma clinically and pathologically. Lymphocytosis and lymphadenopathy spontaneously remitted following cessation of etanercept therapy and have not recurred. Conclusion. Distinction between clinically benign lymphoid proliferations related to antipsoriasis therapy and malignant lymphoma avoids the unnecessary use of anti-lymphoma chemotherapy.