A rare karyotypic event, der(1;15)(q10;q10), which involves the whole long arms of chromosomes 1 and 15, has been reported in patients with various conditions, including acute myelogenous leukemia, myelodysplastic syndrome, polycythemia vera, and multiple myeloma. Only 27 cases of unbalanced der(1;15)(q10;q10) have been documented in the literature as single or complexed chromosomal abnormalities in hematological malignancies. Here, we describe two cases of acute lymphoblastic leukemia with der(1;15)(q10;q10), and review the previous reports. Although more case studies are needed, we suggest that der(1;15)(q10;q10) should be considered a nonrandom chromosomal abnormality in hematological malignancies including both lymphoid and myeloid neoplasms.