TP53 is the most commonly mutated gene in human cancer, but TP53 mutations are present in less than 5% of children with acute lymphoblastic leukemia (ALL) at initial presentation. Mutations are detected more frequently in children with relapsed T-cell ALL, but the potential role of TP53 mutations in relapsed B-lineage childhood ALL is not understood as well. The authors determined the nucleotide sequence of amplified DNA from exons 5 to 8 of the TP53 gene in leukemic cells obtained from 17 children with ALL at the time of first bone marrow relapse. All 17 contained only germline TP53 sequences. Review of the published literature disclosed that TP53 mutations have been found in 22% of cases of relapsed ALL. To understand the role of p53 abnormalities in this clinical setting, it will be important for future studies to analyze cases of relapsed ALL with assays capable of interrogating the functional integrity of the p53 pathway.