Mediastinal large cell lymphoma with sclerosis (MLCLS) is a recently described entity characterized by its locoregional extension, within the anterior mediastinum, and its B cell origin, although the proliferation arises from the thymus. It has been, in the past, often mistaken for other tumors of the anterior mediastinum: invasive thymoma, Hodgkin's disease, poorly differentiated clear cell carcinoma and seminoma, thus leading to inappropriate therapeutic approaches. We diagnosed 6 cases of MLCLS in 1986 and 1987, in 4 males and 2 females, aged 16 to 44 (mean 27). Five of the 6 patients presented with a compressive anterior mediastinal mass, dyspnea, dysphonia, superior vena cava syndrome and parietal protrusion (3 cases). The CT scan confirmed the invasive and compressive characters of the tumor. Two patients initially had disseminated disease. Microscopically, the proliferation was composed of large clear cells, and segmented by bands of sclerosis. Immunologic studies demonstrated the B origin of the tumor cells. All 6 patients received combination therapy with an intensive CHOP protocol (L N H 84 Lyon). The first patient was initially operated, after a false frozen section diagnostic of thymoma. Resistance to chemotherapy (and rapid death within 2 months) was seen in 2 cases. On patient had a partial remission and 3 entered complete remission, of 5+, 10+ and 11 months duration, respectively, with central nervous system relapse in the latter case. Excavation of the tumor on CT scan imaging seemed to be a poor prognostic factor.(ABSTRACT TRUNCATED AT 250 WORDS)