Expression patterns of CD33 and CD15 in normal/reactive bone marrow (n = 13) and in leukemic blasts from patients with acute myeloid leukemia (n = 129) were determined using multiparameter flow cytometry and a standard panel of triple antibody combinations. Five patterns, corresponding to the consecutive stages of myeloid differentiation, were identified [I: CD33-/CD15- (n = 18), II: CD33+/CD15- (n = 43), III: CD33+/CD15 heterogeneous (n = 10), IV: CD33+/CD15+ (n = 50), V: CD33-/CD15+ (n = 8)]. Patients with pattern II had the highest relapse rate and shortest median overall survival (OS, 8 months), but they were also the oldest (median age 72 years) and had the highest frequency of unfavorable cytogenetic aberrations. Pattern V patients had a short OS (median 14 months) even though they were the youngest (median age 50 years), had high remission rate and did not have unfavorable cytogenetics. In multivariate analysis, age, cytogenetics, CD15 expression and the presented immunophenotypic classification were significant for OS (age p = 0.004, cytogenetics p = 0.011, immunophenotype pattern p = 0.024, CD15 p = 0.031). Age (p = 0.001) and immunophenotypic classifications (p = 0.015) were significant for disease-free survival in patients who achieved complete remission.