Hemoglobin alpha chain belongs to the globin family and is involved in oxygen transport from the lung to the various peripheral tissues. Hemoglobin A is comprised of two alpha chains and two beta chains, whereas hemoglobin A2 is comprised of two alpha chains and two delta chains. Immunohistochemical localization of hemoglobin is excellent as an erythroid marker for the detection of immature, dysplastic, and megaloblastic erythroid cells in myeloproliferative disorders, such as erythroleukemia. In contrast, myeloid cells, lymphoid cells, plasma cells, histiocytes and megakaryocytes are negative for hemoglobin alpha antibody. Anti-hemoglobin alpha, combined with CD34, CD117, CD68, and MPO can be helpful in distinguishing between reactive extramedullary hematopoiesis and that seen in neoplastic myeloid disorders in spleen. Anti-hemoglobin alpha is limited to expression by erythroid precursors in bone marrow, thus is of assistance in calculating percentages of erythroid precursors.