The reciprocal t(4;11)(q21;q23) is often described in acute lymphoblastic leukemia (ALL). In some cases, variant or complex t(4;11) has been detected in ALL by cytogenetic analysis, but to our knowledge no molecular study has been reported in these variant translocations. We describe a 27-year-old woman suffering from pre-B-cell ALL with an unusual rearrangement between chromosomes 4 and 11. Because this complex rearrangement involved the 11q23 chromosome band known to be associated with poor prognosis, we performed fluorescence in situ hybridization, Southern blot, and reverse transcription polymerase chain reaction analyses. This confirmed myeloid lymphoid leukemia gene rearrangement and showed the presence of MLL/AF4 fusion transcript. These results showed the importance of molecular analysis that allowed minimal residual disease monitoring in this patient.