BACKGROUND: Multiple myeloma (MM) itself is not considered to be responsible for fever and is not usually listed among the causes of fever of unknown origin (FUO). METHODS: We report three cases of MM presenting with specific fever that we analyze in combination with the three previously published cases. RESULTS: MM could easily be suspected in most, but not all, cases, emphasizing that bone marrow aspiration should be a part of 'standard' FUO investigations. All patients underwent extensive, sometimes potentially harmful, investigations. Conventional treatment of MM produced a sustained improvement in the temperature curve and inflammatory syndrome in all cases within a few months. Fever recurred during nearly all relapses. Six patients died, one after a disease course of more than 8 years. CONCLUSIONS: This series shows that MM may present as a FUO and that useless and hazardous investigations may be avoided given the possibility of specific fever in this disease. Chemotherapy must be considered without much delay after a reasonable work-up to eliminate any associated process, especially infections.