Neoplastic erythroid proliferations may represent a diagnostic challenge owing to the difficulty in characterizing immature erythroblasts. Immunohistochemical expression of aldehyde dehydrogenase (ALDH), carbonic anhydrase isoenzyme I (CA I), and CD2-associated protein (CD2AP) was assessed in 66 bone marrow biopsy specimens and compared with glycophorin A and E-cadherin. ALDH, CA I, and CD2AP labeled neoplastic erythroblasts in most acute erythroid leukemias (AELs) and myelodysplasias and highlighted benign erythroid precursors within normal marrows, erythroid hyperplasias, acute lymphoblastic leukemias (ALLs), blastic plasmacytoid dendritic cell neoplasm, and most acute myeloid leukemias (AMLs). In 2 AELs, CD2AP was negative, and 1 AML lacked identifiable ALDH+ erythroid precursors. Immature erythroblasts were strongly ALDH+, weakly CA I+, weakly CD2AP±, E-cadherin±, and weakly glycophorin A±. AML was uncommonly weakly positive for ALDH, CA I, and CD2AP, and lymphoblasts from 1 ALL were weakly ALDH+. ALDH, CA I, and CD2AP are sensitive and relatively specific immunohistochemical markers for the erythroid lineage. ALDH is superior to glycophorin A and E-cadherin in highlighting immature erythroblasts.