To evaluate the clinical characteristics and treatment outcome of childhood non-Hodgkin lymphoma (NHL) cases with bone marrow involvement, we studied 13 lymphoblastic, 15 small noncleaved cell, and 8 large cell cases with tumor cells in their marrow. They represented 16%, 11%, and 9% of consecutive NHL cases with these respective histologic subtypes. The treatment outcome differed significantly according to histologic subtype--the 5-year event-free survivals (EFS +/- SE) for large cell NHL, small non-cleaved cell NHL, and lymphoblastic NHL cases were 11 +/- 8%, 40 +/- 20%, and 62 +/- 15%, respectively. Increased serum lactate dehydrogenase (LDH) levels (> 500 U/L) were associated with a poorer EFS (5-year EFS, 0% vs. 50 +/- 10%; P < 0.001). Children < or = 5 years of age had a poorer EFS survival than older children (5-year EFS, 14 +/- 9% vs. 44 +/- 10%; P = 0.03). The degree of bone marrow involvement (< 5% vs. > or = 5%) and race were not significantly associated with treatment outcome. Although intensive chemotherapy has substantially improved survival for patients with advanced stage lymphoblastic or small noncleaved cell lymphoma, patients with large cell NHL and associated marrow involvement continue to have a dismal outcome and require novel or more intensive therapy.