Fifty-seven cases of acute myeloid leukemia (AML), which had been subtyped by French-American-British morphologic and cytochemical criteria as myeloid (M1, M2) or monocytic (M4, M5), were retrieved from the files of the Division of Hematopathology, University of Iowa. Corresponding immunophenotyping data were reviewed with attention to the expression of CD14 (MY4) and CD24 (BA-1). Of 20 cases expressing CD24, 19 were M4 or M5, whereas all 14 cases expressing CD14 were of monocyte lineage. Therefore, CD14 was a highly specific (100%) but only moderately sensitive (58%) marker for distinguishing classes M1 or M2 from M4 or M5. By contrast and unexpectedly, CD24 was nearly as specific (97%), but more sensitive (79%) in marking M4 or M5 cells. This appears to be true even though CD24 is apparently not expressed on normal monocytes. When positive staining for either or both antibodies (CD24 or CD14) was considered indicative of a monocytic leukemia, the sensitivity of immunophenotyping in distinguishing M4/M5 from M1/M2 AML rose to 92%, while maintaining 97% specificity. The authors discuss a recent observation that may help explain the unexpected expression of CD24 in monocytic AML. They conclude that the usefulness of CD24 in identifying monocytic AML may exceed that of CD14, and that the use of CD24 and CD14 in combination improves the ability of flow cytometry to distinguish myeloid from monocytic acute leukemias.