Epidemiologic studies of childhood leukemia have made limited use of tumor genetic characteristics, which may be related to disease etiology. We characterized the cytogenetics of 543 childhood leukemia patients (0-14 years of age) enrolled in the Northern California Childhood Leukemia Study, an approximately population-based study comprised primarily of Hispanics (42%) and non-Hispanic Whites (41%), and compared the cytogenetic profiles between these two ethnic groups. Subjects were classified by immunophenotype, conventional cytogenetic characteristics, and fluorescence in situ hybridization findings. The ploidy levels most frequently observed among acute lymphoblastic leukemia patients were high hyperdiploidy (51-67 chromosomes) and pseudodiploidy (34% and 27%, respectively). No ethnic differences in the frequency of 11q23/MLL rearrangements were observed between Hispanics and non-Hispanic Whites. Among B-lineage acute lymphoblastic leukemia patients, the percentage of TEL-AML1 translocations was significantly lower in Hispanics (13%) than in non-Hispanic Whites (24%; P = 0.01). This is the first time that this ethnic variation has been observed in a large number of patients in a defined geographic region, which is consistent with findings from smaller international studies. The mechanistic basis for this 2-fold variation in frequency of TEL-AML1 may be due to ethnic-specific risk factors or genetics and should be explored further.