BACKGROUND: HLA-DR negativity is known to be useful for distinguishing acute promyelocytic leukemia (APL) from other subtypes of AML, but non-APL cases without HLA-DR antigen expression have been reported. The purpose of this study was to evaluate and compare the characteristics of APL, HLA-DR negative non-APL, and HLA-DR positive non-APL cases. METHODS: A total of 114 cases of AML admitted at Ewha Womans University, Mokdong Hospital between March 1997 and June 2006 were included in this study. A diagnosis of AML was made based on the results of morphology, cytochemistry, immunophenotype, cytogenetics, and/or fluorescence in situ hybridization. RESULTS: Among the 114 AML patients, HLA-DR antigen was not expressed in 39 (34%), including 24 non-APL (62%) and 15 APL patients (38%). The HLA-DR negative non-APL group showed higher leukocyte counts and positive rate of CD19 expression than did APL group (P<0.05). The remaining laboratory findings were not statistically different between the HLA-DR negative non-APL and APL groups. CD34 expression was more frequent in the HLA-DR positive non-APL group than in the HLA-DR negative non-APL group and APL group. Of the 24 patients with HLA-DR negative non-APL, 7 patients had disseminated intravascular coagulation and 2 patients showed morphologic features similar to those of APL. CONCLUSIONS: CD19 expression and leukocyte count may be helpful for differentiating HLA-DR negative non-APL from APL. However, the final diagnosis and classification should be confirmed by cytogenetic or molecular studies.