Paraneoplastic pemphigus (PNP) is an autoimmune, mucocutaneous bullous disease associated with underlying malignancies. We report a patient with Waldenström's macroglobulinemia who developed clinical, histological and immunopathological features typical of PNP. The patient was treated twice with i.v. dexamethasone and cyclophosphamide pulse therapy (day 1: cyclophosphamide 500 mg i.v.; day 1-3: dexamethasone 100 mg i.v.) at 3-week intervals. Therapy was continued with oral cyclophosphamide (50 mg/d). Two weeks after initiation of treatment, significant improvement of the cutaneous and mucosal lesions was noted. The therapy also had beneficial effects on the macroglobulinemia in terms of a marked reduction of the IgM lambda serum level. Three months after the second pulse, severe stomatitis recurred but the patient rejected any further systemic therapy. The initial response of the usually recalcitrant mucosal and skin lesions of PNP makes dexamethasone/cyclophosphamide pulse therapy an interesting therapeutic option.