About 25% of the patients with the translocation t(11;19)(q23;p13.3)/KMT2A-MLLT1present three-way or more complex fusions, associated with a worse prognosis, suggesting that a particular mechanism creates functional KMT2Afusions for this condition. In this work, we show a cryptic three-way translocation t(9;11;19). Interestingly, long-distance inverse polymerase chain reaction sequencing revealed a KMT2A-MLLT1and the yet unreported out-of-frame SEC16A-KMT2Afusion, associated with low SEC16Aexpression and KMT2Aoverexpression, in an infant with B-acute lymphoblastic leukemia presenting a poor prognosis. Our case illustrates the importance of molecular cytogenetic tests in selecting cases for further investigations, which could open perspectives regarding novel therapeutic approaches for poor prognosis childhood leukemias.