Accurate diagnosis of monocytic neoplasms often is dependent on quantitating monoblasts, promonocytes, and monocytes. However, distinguishing these populations by morphologic assessment alone can be difficult and subject to significant intraobserver variability. We evaluated a 4-color flow cytometry technique using different anti-CD14 antibodies that recognize the MO2 and MY4 epitopes to identify monoblasts, promonocytes, and monocytes. Normal control specimens and 18 cases of monocytic neoplasia were evaluated and results correlated with morphologic findings. We found the MY4 epitope first appearing at the early promonocyte stage and the MO2 epitope appearing only on mature monocytes after the promonocyte stage. Expression of the MY4 and MO2 epitopes by neoplastic monocyte populations was found to usually parallel the normal monocyte differentiation patterns, although exceptions were noted. Our study suggests that 4-color flow cytometry may be an especially useful adjunct for morphologically difficult cases by providing an immunophenotypic measure of neoplastic monoblasts and promonocytes.