Primary mediastinal (thymic) large B-cell lymphoma is a discrete clinicopathologic subtype of diffuse large cell lymphoma recognized in the revised European-American lymphoma classification. It is an uncommon but not rare tumor with worldwide distribution. For the clinician, the occurrence of this aggressive, invasive, yet localized neoplasm arising in an unusual site in a cohort of young adult patients (frequently women) in whom large cell lymphoma is infrequent is noteworthy. The pathologist is impressed both by the characteristic sclerosis and the unusual surface immunoglobulin (SIg)-negative B-cell phenotype of a tumor arising in a T-cell organ (thymus). The phenotype is that of a B-cell subset resident in the thymic medulla. The pattern of spread resembling that of extranodal lymphoma and the excellent response to appropriate combination chemotherapy and irradiation further support the discrete character of mediastinal large cell lymphoma, and provide a practical reason for recognizing the entity. Poorly chosen or executed primary therapy can lead to rapid tumor growth or regrowth with treatment failure and death, but a reassuringly high cure rate follows appropriate management.