We report a case of acquired von Willebrand syndrome in association with multiple myeloma, diagnosed in a 54 year-old man suffering from sudden onset of mucocutaneous bleeding. The acquired von Willebrand syndrome is a rare bleeding disorder with laboratory findings similar to those of inherited von Willebrand disease. Diagnosis, etiology and pathophysiology of acquired von Willebrand syndrome are reviewed to establish a differential diagnosis with inherited von Willebrand disease. Identification of the underlying disease responsible for the acquired von Willebrand factor defect and the bleeding diathesis is necessary to choose among the therapeutic options the appropriate treatment.