Two patients with multiple myeloma are described in whom an unusual complication developed: pleural effusion containing myeloma cells. There are 7 previously reported cases of myeloma in the English literature with this type of effusion. Pleural effusion in myeloma may be due to plasma cell infiltration of the pleura, congestive heart failure, pulmonary embolism, nephrotic syndrome, and second neoplasms. In view of these multiple etiologies, diagnostic thoracentesis should be performed in order to treat the effusion appropriately.