The independent significance of CD10 expression in childhood acute lymphoblastic leukemia (ALL) is uncertain because most studies have not adjusted for other risk features, such as age and immunophenotype, or for treatment effects. We reassessed the clinical importance of CD10 expression in patients who received highly effective contemporary treatment. CD10 antigen was detected in blast cells from 384 of 408 patients (94%) with B-lineage ALL and 36 of 90 (40%) with T-cell ALL. In the B-lineage subgroup, CD10 expression was associated with favorable presenting features: age > or = 1 year, lower leukocyte count (< 50 x 10(9)/l), and leukemic cell DNA index > or = 1.16 or hyperdiploidy > 50 chromosomes. One-half of the patients with CD10- B-lineage ALL had 11q23 chromosomal abnormalities. Separate analysis of the marker in T-cell ALL revealed no differences between CD10+ and CD10- cases in clinical features or karyotypic patterns, with the exception of a lower frequency of central nervous system leukemia and a higher frequency of 9p abnormalities in the former subgroup. CD10+ T-cell cases were also significantly more likely than CD10- cases to coexpress CD21, CD1, CD4, or CD8. Lack of CD10 expression was independently associated with an adverse prognosis in T-cell ALL (p = 0.02). However, for the larger subgroup of patients with B-lineage ALL, CD10 expression has no independent prognostic significance.