Patients with double-mutatedCEBPA(CEBPAdm) AML were stratified into favorable risk group, however, few studies have investigated the heterogeneity of differentCEBPAdm types in detail. In this study, we analyzed 2211 newly diagnosed AML and identifiedCEBPAdm in 10.8% of the patients. Within theCEBPAdm cohort, 225 of 239 patients (94.14%) presented with bZIP region mutations (CEBPAdmbZIP) while 14 of 239 patients (5.86%) without bZIP region mutation (CEBPAdmnonbZIP). Analysis of the accompanied molecular mutations showed statistically different incidences of GATA2 mutations between theCEBPAdmbZIP group and theCEBPAdmnonbZIP group (30.29% vs 0%). In the analysis of outcomes, patients withCEBPAdmnonbZIP were associated with shorter overall survival (OS) censored at hematopoietic stem cell transplantation (HSCT) during CR1 compared to those withCEBPAdmbZIP (hazard ratio (HR) = 3.132, 95% confidence interval (CI) = 1.229–7.979,P= .017). Refractory or relapsed AML (R/RAML) patients withCEBPAdmnonbZIP were associated with shorter OS compared to those withCEBPAdmbZIP (HR = 2.881, 95% CI = 1.021–8.131,P= .046). Taken together, AML withCEBPAdmbZIP andCEBPAdmnonbZIP showed different outcomes and might be regarded as distinctive AML entities.