Children with primary immunodeficiency or chromosomal breakage syndromes are at increased risk of developing non- Hodgkin lymphomas; they cannot tolerate standard chemotherapy regimens. We report two children with diffuse, large, B-cell lymphoma; one had ataxia telangiectasia and one had common variable immunodeficiency. Both were given rituximab, 1 as monotherapy and 1 in combination with a reduced CHOP regimen. Complete remission was obtained in each patient. Use of rituximab as a first-line monotherapy or in conjunction with reduced chemotherapy should be considered to reduce cytotoxic effects.