Three cell populations with different DNA indices were demonstrated in a case of biphenotypic terminal transferase (TdT)/myeloid-positive acute leukemia which had developed from a pre-leukemic diploid population also expressing biphenotypic features. At the time of development of acute leukemia, flow-cytometric analysis revealed expression of TdT by the diploid, the tetraploid, and the near-triploid cells, but only the tetraploid cells carried the myeloid-specific M2 antigen. Cytogenetic analysis showed four stemlines, diploid, tetraploid, tetraploid with del(2), and near-triploid with del(2) and variable chromosome losses. In vitro treatment with retinoic acid induced the expression of the M2 antigen by the diploid cells as well. This in vitro result is consistent with a myeloid differentiation commitment of the pluripotent leukemic stem cell.