A 76-year-old woman who had a history of chronic lymphocytic leukemia/small lymphocytic lymphoma for the last 7 years was treated with Rituxan plus CVP (cyclophosphamide, vincristine, and prednisone). Treatment was completed in May 2006. The patient remained in remission until mid-December 2011 when she presented with markedly elevated white blood cell counts in a routine clinical follow-up. At the time, she had mild anemia (hemoglobin, 11.2 g/dL) and thrombocytopenia (platelets, 135 × 10*9/L) but marked leukocytosis (white blood cells, 68 × 10*9/L). Laboratory differential count revealed 26% lymphocytes and 62% “unclassified cells.” Her lactate dehydrogenase level was 2422 U/L. The peripheral blood smears (panel A) showed marked leukocytosis with cocirculation of 2 apparent lymphoid populations: one blastic population (intermedium in size, with a high nucleus-to-cytoplasm ratio, disperse chromatin, and prominent nucleoli; see arrows) and the other mature-appearing lymphocytes (small in size, with scanty cytoplasm and clumped chromatin). Occasional smudge or basket cells were seen. Flow cytometric analysis demonstrated 2 distinctive populations with side scatter and CD45 expression characteristics (panel B). The blast population (dim CD45) expressed CD19, CD10, CD34, cytoplasmic CD22, and terminal deoxynucleotidyltransferase without surface immunoglobin, while the lymphocyte population (bright CD45) displayed a dim surface ?-restricted monotypic B-cell population with expression of CD19, CD20, and aberrant expression of CD5. Conventional karyotype analysis yielded 2 clonal populations, 46,XX,t(9;22)(q34.1;q11.2)[5] and 46,XX,t(3;6;10)(p21;q25;q22)[7], representing precursor B acute lymphoblastic leukemia and chronic lymphocytic leukemia, respectively.