We report a 2-year-old boy with B-cell acute lymphoblastic leukemia. Cytogenetic studies at diagnosis with R-banding showed a 46,XY,ins(12;3)(p13;q?21q?22)/46,XY karyotype. Fluorescence in situ hybridization with TEL/AML1 probes and chromosome paints revealed complex rearrangements. The TEL/AML1 fusion gene was located on the derivative chromosome 21 but a segment of the long arm of a chromosome 3 was inserted between the proximal part of the short arm of the derivative chromosome 12 and the reciprocal part of the AML1 gene. This is consistent with an insertion of chromosome 3 into chromosome 12 after the t(12;21) took place, therefore indicating a probable secondary event due to clonal evolution.