Mediastinal tumor was found in both acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). Most cases showed the T-cell phenotype. We query whether these two diseases are in fact different disorders or merely different stages of the same disease. Twelve ALL patients with a mediastinal mass and eleven NHL patients with a mediastinal mass under 15 years of age were studied with respect to cytogenetics, immunophenotype, genotype and clinical features. Clonal chromosome abnormalities were found in 75% (9/12) of the ALL patients and 100% (11/11) of the NHL patients. Of the 20 patients with chromosome abnormalities, 12 (60%) had translocations involving 14q11-13 and 7q35 (8 ALL, 4 NHL). t(9;17)(q34;q23) was found only in 3 patients with NHL. All showed the T-cell phenotype except two, who had none of the chromosomal abnormalities frequently detected in T cell ALL/NHL. In T-cell patients, immunophenotypical staging of ALL showed a predominance of early and common thymocyte phenotypes while that of NHL showed a predominance of common thymocyte phenotypes. All 7 of the T-cell patients examined showed rearrangements of the T-cell receptor beta chain gene. On the other hand, two non-T-cell, non-B-cell patients showed no rearrangement. There were no apparent clinical differences between ALL and NHL patients in age (median 8.6 vs 8.9 years), sex ratio (F/M 9/3 vs 7/4) or in the rate of complete remission (90% vs 100%). Our study demonstrated no relevant clinical, prognostic, or immunophenotypic differences between ALL and NHL with mediastinal mass.(ABSTRACT TRUNCATED AT 250 WORDS)