One of the highest incidences of acute lymphoblastic leukemia (ALL) in the world has been reported in Mexico City. In the current study (26 cases), the frequencies of the most frequent genetic rearrangements TEL-AML1, MLL/AF4, BCR-ABL (major and minor) in ALL in children from Mexico City were determined. For the ALL, the frequency of MLL/AF4 was 65.4%, for TEL-AML1 and that of BCR/ABL was 3.8%. Only 6 of the 17 children with the MLL/AF4 rearrangement were less than 26 months old. The frequency reported for MLL/AF4 in Mexican children with ALL is one of the highest worldwide. These findings could potentially explain the higher frequency of ALL with poor prognosis for children in Mexico City.