Primary mediastinal diffuse large B-cell lymphoma is a quite rare clinicopathologic entity. Molecular analysis shows it to be distinct from other types of diffuse large B-cell lymphoma, and some retrospective analyses suggests that it may respond better to third-generation chemotherapy regimens than to the more commonly used CHOP. The addition of rituximab could reduce these differences; the role of consolidation with local radiotherapy, which is often used to treat residual mediastinal masses, remains. The real role of FDG-PET scanning requires prospective studies, and it is hoped that this may allow the de-escalation of radiation therapy accordingly to yield reliable prognostic information.