Discrepancies in the literature on acute leukemia blast cell immunophenotypes are sometimes related to differences between the epitopes recognized by various monoclonal antibodies (MoAb) in the same cluster of differentiation. CD15 is one example of such a variation. CD15 expression has been reported in 1.6% to 39% of acute lymphoblastic leukemias (ALL). We studied the expression of CD15 using 10 different commercially available anti-CD15 MoAbs and we observed three different expression patterns using anti-CD15 MoAbs by flow cytometry in 158 cases of ALL: Smy15c was found in 70% of B lineage ALLs, Smy15a and FMC-13 in 30 to 40% of cases and all others in less than 9% of B-ALL cases (p < 0.0001). In T lineage ALLs, Smy15c, Smy15a and FMC-10 identified CD15 in 30% of the cases and all others in less than 8% of the cases. Logistic regression revealed that Smy15a, CD34 and CD14 correlated significantly with Smy15c expression. We conclude that CD15 MoAbs have to be chosen carefully when ALL immunophenotype and subsequent studies of prognostic significance are performed particularly in assessing multiphenotypic ALLs.