Structural rearrangements involving the short arm of chromosome 12 are common in acute lymphoblastic leukemia (ALL) and often involve the TEL locus at 12p13. The balanced t(12;17)(p13;q12) is a rare but recurrent aberration in ALL. Whereas the TEL gene has been postulated as a likely candidate for involvement in the t(12;17), the precise molecular consequences of this translocation have not yet been elucidated. We identified a t(12;17) in 2 of 398 childhood ALL patients karyotyped at presentation in our institute. Both cases had a precursor-B immunophenotype and were CD10 negative and CD33 positive. Fluorescence in situ hybridization excluded involvement of the TEL locus in the t(12;17) and provided no evidence for concomitant cryptic deletion of the 12p commonly deleted region. Comparison of these and previously published cases demonstrates that the translocation predominately occurs in children and young adults with precursor B-ALL and is typically characterized by low CD10 expression and high CD33 expression. Our data support the involvement of a new locus telomeric to TEL in the pathogenesis of t(12;17)-positive ALL.