The heterogeneity of disease conditions in acute leukemia (AL) requires the most discriminative procedures for a differential diagnostic classification. Selected cases of AL, representative of lineage fidelity, multilineage phenotype and phenotypic switch, are reviewed to document that the diversity of the leukemic cells (lineage involved, maturation stage, aberrant markers), although not always characterizable by morphological differences, is reflected by a variety of immunophenotypes which may be efficiently characterized by flow cytometry to obtain a precise diagnosis.