Hemophagocytic syndrome (HPS) is an uncommon reactive disorder characterized by proliferation of histiocytes that actively engulf other hematopoietic cells causing cytopenia. It complicates several diseases including hematological neoplasias. We report the case of a 54-year-old woman who was admitted to our hospital with fever of unknown origin. Her clinical picture was characterized by renal failure, splenomegaly and pancytopenia. Findings on bone marrow examination showed HPS associated with multiple myeloma. A review of the literature revealed that only one case has previously been published.