Large B-cell lymphoma manifesting in the mediastinum shows distinctive clinical and immunophenotypic features and is recognized as a unique type of large B-cell lymphoma in the Revised European-American Lymphoma classification. Fifty-one cases of primary mediastinal large B-cell lymphoma were retrieved from the immunodiagnosis laboratory database files and were stained with anti-CD30 (Ber-H2). Of the 51 cases, 35 (69%) stained for CD30. This staining ranged from strong membrane staining of all or almost all of the neoplastic cells to positivity of rare individual cells. Eleven cases (22%) were negative; 4 (8%) were equivocal. Only 1 case was uninterpretable owing to B-5 fixation and lack of a positive internal control. Thus, the majority of mediastinal large B-cell lymphomas express the Hodgkin marker CD30. This finding may result in misdiagnosis of large cell lymphoma as Hodgkin disease.