In discussions concerning the evaluation of macrocytic anemia, the importance of examining the peripheral smear is often emphasized.11,17 However, compliance with this recommendation is poor among physicians other than hematologists. To the skilled examiner, a variety of smear findings may provide diagnostic clues. For example, the presence of oval macrocytes suggests a megaloblastic disorder, whereas the presence of stomatocytes is significantly more common among patients with macrocytosis caused by alcoholism than among Cbl-deficient patients.18 The presence of hypersegmented neutrophils has been said to be highly sensitive and specific for the diagnosis of megaloblastic anemia.11,19 For example, in one study20 in which hypersegmentation was defined as the presence of at least 1 neutrophil with 6 lobes or more, the sensitivity of this finding for the diagnosis of megaloblastic anemia was 98%. However, patients in this study had unequivocal megaloblastic changes on bone marrow examination and low serum vitamin concentrations. In more recent studies21,22 of patients with mild Cbl deficiency, the finding of neutrophil hypersegmentation was neither sensitive nor specific. It is doubtful that examination of the smear, especially by physicians other than hematologists, will avoid the need for use of less observer-dependent tests in the evaluation of macrocytic anemia.