The laboratory characterization of acute leukemia has evolved as new technologies have emerged and been applied in the routine evaluation of these hematologic malignancies. With the use of morphology, cytochemistry, flow cytometry, cytogenetics, and molecular genetics, it is possible to characterize acute leukemias in an extremely sophisticated and (ideally) therapeutically rational manner. Such routine approaches have unraveled, in part, the extreme and sometimes bewildering heterogeneity of the acute leukemias, with the identification of increasingly numerous subtypes. Much of this complexity is defined by the underlying genetic lesions, the determination of which is assuming an even greater role in the definition of specific entities. For example, more than 200 different recurrent cytogenetic abnormalities have been described in one broad category of acute leukemia, the acute myeloid leukemias (AMLs). 1 Of note, these karyotypically detectable abnormalities occur in just more than half of all AMLs, with the remaining approximately 45% of these cases having normal cytogenetics. Molecular genetic insights into the latter category have accelerated in the past 5 years, with up to 80% of cases with a normal karyotype already revealing fascinating submicroscopic molecular aberrations. 2 This will yield additional tiers of complexity, accompanied, hopefully, by clarity of the underlying pathogenic mechanisms and, ultimately, improved therapy.

Nevertheless, the major initial decision to be made when assessing an acute leukemia is whether it is lymphoid or myeloid because this usually straightforward assignment of lineage is central to guiding remission induction chemotherapy and subsequent therapy. Whereas morphologic studies and cytochemistry were originally the primary tools used in such decisions, they have been largely if not completely superceded