Primary mediastinal B-cell lymphoma (PMBCL) is a clinicopathological entity with aggressive behavior. Retrospective evaluation suggests the need for intensive chemotherapy programs. From 1997 to February 2003, a total of 11 cases of previously untreated PMBCL with sclerosis were treated at our institution with 5 courses of intensified CHOP (ICHOP) regimen and mediastinal irradiation. Three patients were submitted to high-dose chemotherapy with peripheral-blood stem-cell support, followed by radiotherapy, because of intermediate-risk age-adjusted International Prognostic Index at diagnosis. After a median follow up of 30 months, all patients but one are in continuous complete remission (CR), and overall survival is 100%.