Many patients with multiple myeloma tend to have low serum cobalamin. The cause of this remains unclear. The important issue is whether cobalamin therapy should be used or not. We describe one case of megaloblastic erythropoiesis and multiple myeloma, and refer to some of the few studies describing the subject. Most of the patients with multiple myeloma are elderly, and the frequency of hypo- and achlorhydria is therefore increased. It has been demonstrated that cobalamin uptake and consumption is higher in myeloma cells than in normal bone marrow cells, and that cobalamin may be required for paraprotein synthesis. These facts may suggest that patients with multiple myeloma are more vulnerable to developing megaloblastic anemia than others. Our patient received cobalamin therapy in addition to cytostatic therapy for multiple myeloma without complications. However, we cannot exclude that cobalamin therapy may accelerate multiple myeloma; this should be considered when such therapy is given. However, accurate guidelines require more studies.