CD200, an immunoglobulin superfamily membrane glycoprotein, is expressed in a number of B cell lymphoproliferative disorders, including primary mediastinal large B cell lymphoma, but not diffuse large B cell lymphoma, based on a preliminary study. Here, we compare the expression of CD200 with other markers of primary mediastinal large B cell lymphoma, including MAL and CD23, in formalin-fixed, paraffin-embedded histologic sections from a series of 35 cases of primary mediastinal large B cell lymphoma and 30 cases of diffuse large B cell lymphoma. CD200 exhibits the greatest staining sensitivity of the markers studied: 94%, compared with CD23 (69%), MAL (86%), TRAF (86%), and REL (77%). It exhibits staining specificity of 93%, similar to that of CD23 (93%) and MAL (97%), and greater than that of TRAF (77%) and REL (83%). We conclude that CD200 is a practical and useful marker for the diagnosis of primary mediastinal large B cell lymphoma.