We describe the case of a 40-year-old man whose disease was initially diagnosed as acute myelocytic leukemia. The patient achieved remission with chemotherapy, but relapsed shortly afterwards with an acute T-cell lymphoblastic leukemia. He died of intracranial bleeding. Karyotyping analysis showed a del(9p?) as a common abnormality in the leukemic cells at onset and relapse. Fluorescence in situ hybridization analysis demonstrated allelic loss of the CDKN2A gene in cells from both stages of the disease. At relapse the leukemia cells had additional abnormalities such as add(1)(p36) and del(12)(p11). We postulate that the loss of CDKN2A is involved in leukemogenesis but does not determine the lineage of the leukemic cells. Instead, abnormalities of genes at 1p36, 12p11, or both may be involved in driving a lymphoid phenotype.