A 50-year-old African American man with sickle cell disease (SCD), transfusion-associated iron overload and stage III chronic kidney disease was admitted to our hospital with fever, shortness of breath and tachypnea. He was found to have bilateral lung crackles, leukocytosis and bilateral basilar infiltrates on chest radiography. Our patient reported a 15-pound weight loss and an increased frequency of bone pain over a period of six months. His medications included hydroxyurea and deferasirox. He was treated for painful sickle crisis and community-acquired pneumonia with analgesics, oxygen and antibiotics. He showed an initial improvement in clinical condition. He received repeated blood transfusions for his worsening anemia but did not show a subsequent increase in his hematocrit. His refractory anemia workup did not support any active bleeding or hemolysis. His reticulocyte count was 1.2% and his parvovirus B19 antibody assay was negative. A peripheral smear showed anisocytosis and Howell-Jolly bodies, but no schistocytes. Our patient deteriorated four days after admission, with drowsiness, disorientation and slurred speech. A physical examination was unrevealing and a neurological examination showed no focal deficits. His electrolytes, blood urea nitrogen, creatinine, blood and urine cultures and brain imaging were indeterminate. His serum ammonia level was 81 μmol/L; he was started on lactulose with no clinical response. His opioid medications were decreased and he was given naloxone without improvement in his mental status. By the seventh day, he was stuporous. His family began to consider a 'comfort measures only' goal of care. This case was a diagnostic quandary. To decipher the cause of the refractory anemia, bone pain and change in mental status we focused on the surprising finding of a serum anion gap (AG) of zero. His outpatient AG over the last six months had been between three and four. Further testing revealed that he had decreased serum albumin (2 g/dL), elevated serum protein (12.6 g/dL) and increased gamma globulin (7.5 g/dL). Immunofixation showed an immunoglobulin G monoclonal protein with kappa light chain specificity. Bone marrow analysis revealed 70% plasma cells, confirming the diagnosis of multiple myeloma (MM). He was treated with dexamethasone (Decadron) and melphalan hydrochloride and made significant improvement, returning to his baseline functional status within 14 days.