The majority of cases of acute leukemia belong to a specific lineage origin, either lymphoid or myeloid, and therefore are classified as acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML), based on morphologic features and cytochemical and immunophenotypic profile of the blast cells. A minority of acute leukemias however, show no clear evidence of differentiation along a single lineage. These are now classified under acute leukemias of ambiguous lineage by the most recent WHO classification and account for <4% of all cases of acute leukemia [1]. They include leukemias with no lineage specific antigens (acute undifferentiated leukemias) and those with blasts that express antigens of more than one lineage to such degree that it is not possible to assign the leukemia to any one particular lineage with certainty (mixed phenotype acute leukemias). The latter can either be leukemias with two distinct populations of blasts, each expressing antigens of a different lineage (historically referred to as "bilineal" leukemias) or a single blast population expressing antigens of multiple lineages (historically referred to as "biphenotypic" acute leukemias) [2]. Acute leukemias of ambiguous lineage may harbor a variety of genetic lesions. Those with t(9;22)(q34;q11) or translocations associated with mixed lineage leukemias (MLL) gene, i.e., t(11;V)(q23;V), occur frequently enough and are associated with distinct features, that are considered as separate entities according to the recent WHO classification. Co-expression of myeloid and B-lymphoid antigens is most common in mixed phenotype acute leukemia (MPAL), followed by co-expression of myeloid and T-lymphoid antigens, accounting for 66-70% and 23-24% of MLLs, respectively. Coexpression of B- and T-lineage associated antigens or antigens of all three lineages is exceedingly rare, accounting for <5% of MLLs [3,4]. The requirements for assigning more than one lineage to a single blast population has been established by current WHO classification [1].