Renal dysfunction is a common comorbidity of multiple myeloma. However, tumor lysis syndrome is a rare cause of renal dysfunction in multiple myeloma. Elotuzumab is a newly US FDA-approved monoclonal antibody used in the treatment of refractory multiple myeloma. To our knowledge, elotuzumab has not been associated with a case of tumor lysis syndrome. We present the case of a patient who developed clinical tumor lysis syndrome 1 week after treatment with elotuzumab accompanied by renal failure with hyperphosphatemia, hyperkalemia, and profound hyperuricemia. His course was further complicated by significant epistaxis from the accumulation of dabigatran in acute renal failure. In spite of treatment with rasburicase and hemodiafiltration, the patient decompensated and eventually died. Risk factors for the development of tumor lysis syndrome in multiple myeloma are discussed.