The abnormality in the translocation of chromosomes 4 and 11 (t[4;11]) has been characteristically associated with calla-negative CD15(+) acute lymphoblastic leukemia (ALL) of early pre-B-cell origin. Transformation of a lymphoblastoid to a monoblastoid morphologic structure has rarely been described at relapse in these cases; however, these cases have lacked flow cytometric immunophenotyping (FCI) and genotypic studies (GS) to define the immunophenotype of and the presence of a B-cell gene rearrangement in the monoblastoid component. We report a case of CD15(+), CD10(-) ALL of early pre-B-cell origin defined by morphologic testing and FCI with the t(4;11) abnormality. At relapse, the morphologic testing, enzyme cytochemistry, and FCI data were characteristic of monoblastic leukemia. The t(4;11) abnormality persisted with associated additional chromosomal abnormalities, and the monoblasts contained a B-cell gene rearrangement by GS. These findings support the concept that both processes arose from a multipotential progenitor cell.