We compared the expression of CD123, the α chain of the interleukin-3 receptor, on normal B-cell precursors in bone marrow (“hematogones”) from 75 specimens and on leukemic blasts in 45 newly diagnosed B-acute lymphoblastic leukemias (B-ALL) cases. We found that the less mature hematogones (dim CD45+) that express CD34 lack CD123 expression, whereas the more mature hematogones (moderate CD45+) lack CD34 but always express CD123. In contrast with this discordant pattern of CD34 and CD123 expression in hematogones, blasts in 41 (91%) of 45 cases of B-ALL showed concordant expression of the 2 antigens: 80% (36 of 45) cases expressed both antigens, whereas 11% (5 of 45) expressed neither. We found that these distinct patterns of CD34/CD123 expression on hematogones (discordant) and B-ALL blasts (concordant) remain stable after chemotherapy and are useful in differentiating small populations of residual blasts from hematogones that may be simultaneously present.