Paraffin-embedded diagnostic biopsy materials from a large cohort of pediatric and adolescent patients with mature B-cell non-Hodgkin's lymphoma (NHL) treated on the Children's Cancer Group arm of an international cooperative trial were studied to determine their phenotypic features and the feasibility of using targeted bioimmune therapies. There were 345 patients eligible for analysis: 208 with Burkitt's lymphoma (BL), 43 with high-grade B-cell lymphoma, Burkitt-like (HGBL), and 94 with diffuse large B-cell lymphoma (DLBCL). Samples were immunophenotyped centrally using a standard panel that included CD20, CD79a, CD3, and CD45RO. Additional staining with CD22 was performed on a subset of cases. Immunophenotypic studies showed positive staining with CD20 in 100% of cases of BL and HGBL and in 98% of cases with DLBCL. CD22 expression was present in all cases of BL and DLBCL and in 87% of cases HGBL. This study indicates that immune-based therapies such as rituximab and ibritumomab-tiuxetan (anti-CD20) and epratuzumab (anti-CD22) are feasible in pediatric cases of mature B-cell NHLs.