Lineage switch is a very rare event in blastic crisis of chronic myelogenous leukemia (CML-BC). To our knowledge, only three cases of lineage switch between lymphoid and myeloid/myelomonocytic lineages have been reported in the literature. Here, we report a novel case of imatinib-resistant CML-BC, in which the blast lineage switched from biphenotypic to B-lymphoid.