The authors studied six adult patients with acute leukemia with these unusual characteristics: unclassifiable morphology and undifferentiated cytochemistry by French-American-British (FAB) criteria; concurrent expression of CD13 (and CD33) myeloid and early T-cell CD7 immune markers; no evidence of T-cell lineage commitment as determined by T-cell receptor beta (beta), gamma (gamma), and delta (delta) chain gene rearrangement study and cytoplasmic CD3 epsilon expression; and no evidence of myeloid cell lineage commitment, as shown by absent myeloid-specific c-fms proto-oncogene expression and negative myeloperoxidase ultrastructural staining (one case). Clinically, these diagnostic features matched with a poor prognosis, being associated with refractoriness to treatment, relapse and progression of disease, antecedent hematologic abnormality, and other malignancy. These cases may represent a distinct stem cell leukemia syndrome deserving immediate recognition and a nonconventional chemotherapeutic approach.