We used flow cytometry to determine the CD58 expression on nonmalignant B cells at different stages of maturation in the bone marrow and compared it with that of blasts in adult and pediatric precursor B-cell acute lymphoblastic leukemia (B-ALL). The mean fluorescence intensity (MFI) of CD58 expression decreased significantly as nonmalignant B cells differentiated in the bone marrow from an early to a mature stage. Few nonneoplastic B cells at a mid or mature stage of development expressed CD58 MFI values comparable to those seen in leukemic cases. Early-stage nonneoplastic B-cell precursors expressed relatively higher CD58 levels, which frequently overlapped with the variable level of CD58 expression observed among leukemic blasts. As a group, however, the malignant precursor B-ALL cells showed significantly higher expression of CD58 than nonmalignant B-cell populations at any maturational stage. These findings support the potential usefulness of CD58 expression in the diagnosis and monitoring of precursor B-ALL, but only when blasts express high levels of CD58.