Chromosome 13 aberrations, particularly in the region 13q12 approximately q14, are common events in hematological neoplasms that have a clinical significance in many cases. However, although chromosome 13 aberrations are a nonrandom event in childhood acute lymphoblastic leukemia (ALL), their biological and clinical associations are limited. We have studied a consecutive series of 277 cases of childhood ALL, including 33 initially at relapse, by conventional cytogenetic analysis. In 20 cases, a chromosome 13 aberration that involved the region 13q12 approximately q14 was detected at some point during the disease. An aberration was identified in 15 of 244 (6.1%) presentation cases and 7 of 54 (13%) relapsed cases, of which in 11 cases it was shown that the abnormality arose as a secondary karyotypic event. To further characterize the cases, fluorescence in situ hybridization (FISH) using the commercially available probes LSI 13 (RB1) and D13S25 (both 13q14) was undertaken. These analyses provided additional evidence for the secondary nature of many events and suggested that 13q14 deletions may confer a growth advantage in culture because the percentage of cells containing 13q14 deletions detected by FISH was often lower than that detected by G-banding. Since 13q12 approximately q14 aberrations in childhood ALL frequently occur as secondary events, these results imply that the abnormality has implications for disease progression.