Plasma cell leukemia (PCL) is an aggressive disease with poor prognosis and a median survival of only 2-6 months. Currently, no standard therapy is available, but intensive polychemotherapy appears to be more effective than the conventional melphalan plus prednisone. However, the efficacy of thalidomide in PCL has not yet been widely evaluated. Recently, treatment with thalidomide has been reported to yield promising results in refractory multiple myeloma. Here, we report on a patient with primary PCL in whom first-line treatment with thalidomide/dexamethasone resulted in a rapid response and achievement of a very good partial remission.