A lineage switch in leukemia, in which the leukemic cell lineage at onset converts to another lineage at a later time, is an uncommon type of hybrid (mixed) leukemia regarded as a variation of bilineage leukemia. We present a case of a 60-year-old female diagnosed with precursor B cell acute lymphoblastic leukemia (ALL), whose markers in flow cytometry shifted from their original status of CD19+, 22+, 79a+, 13+, HLA-DR+, and TdT+. Although her bone marrow achieved remission after induction therapy, there was a small residual population of leukemic cells in the liver. Residual disease was proved by biopsy and pathologically shown to have an immature phenotype of CD5+, CD10-, CD20-, CD79a- and myeloperoxidase negativity. Two weeks after liver biopsy, blast cells progressively appeared in the peripheral blood; these cells had a monocytoid morphology and phenotype (CD13, 14) but were accompanied by myeloid (CD33) and lymphoid (CD2, 4, 20) cells. Markers CD7, 10 and 19 were negative by flow cytometry. This phenotypical conversion from B-ALL to hybrid leukemia featuring monocytoid characteristics is known as a lineage switch. This case suggests that leukemic subclones tend to carry out dedifferentiation, occasionally in extramedullary sites, which serve as a hotbed for the selection of resistant clones.