The treatment outcome for infant acute lymphoblastic leukemia (ALL) with positive MLL gene rearrangements remains poor. We analyzed whether additional chromosomal abnormalities (ACA) other than 11q23 translocation could affect the disease behavior and its prognosis. Eighteen of seventy-four patients with infant acute lymphoblastic leukemia showed ACA, including three-way translocations in four, other novel translocations in four, and complex structural chromosomal changes in four. Only age less than 6 months and positive central nervous system leukemia were significant prognostic factors by multivariate analysis. However, overall survival rates were worse in patients with ACA compared to those with non-ACA. Genetic alterations induced by additional chromosomal changes may be associated with disease progression and poorer overall survival rates in infants with MLL-rearranged ALL.