CD20 expression is associated with inferior survival in adults with ALL. Preliminary reports indicate that regimens incorporating rituximab improve outcome in this subgroup. We analyzed the prognostic impact of CD20 in 353 children with B-cell precursor ALL treated between 12/20/91 and 5/17/99 on three consecutive St. Jude Total Therapy studies. CD20 expression (>20%) was found in 169 patients (48%). Expression was higher in patients between 1 and 10 years (51% of 252 patients), as compared to those less than 1 year of age (7% of 15 patients) or more than 10 year old (43% of 86 patients), p=0.0008. African American patients were more likely to express CD20 (66%), as compared to Caucasians (45%) or other ethnic groups (45%), p=0.047. None of 14 patients with MLL-AF4 expressed CD20. There was no association between CD20 expression and E2A-PBX, TEL-AML1, ploidy, WBC at diagnosis, or gender. In contrast to the experience in adult ALL, our patients with CD20 expression tended to have a better treatment outcome than those without the expression: 5-year EFS 84% ± 2.9% versus 78% ± 3.1% (p=0.08); 5-year overall survival 88% ± 2.5% versus 83% ± 2.8% (p=0.13). This data suggest that CD20 expression is not associated with inferior outcome in pediatric patients treated with contemporary regimens.