PurposeClassical Hodgkin lymphoma (cHL) is characterized by a low percentage of tumor cells in a background of diverse, reactive immune cells. cHL cells commonly derive from preapoptotic germinal‐center B cells and are characterized by the loss of B‐cell markers and the varying expression of other hematopoietic lineage markers. This phenotypic variability and the scarcity of currently available cHL‐specific cell surface markers can prevent clear distinction of cHL from related lymphomas.Experimental designWe applied the cell surface capture technology to directly measure the pool of cell surface exposed proteins in four cHL and four non‐Hodgkin lymphoma (NHL) cell lines.ResultsMore than 1000 membrane proteins, including 178 cluster of differentiation annotated proteins, were identified and allowed the generation of lymphoma surfaceome maps. The functional properties of identified cell surface proteins enable, but also limit the information exchange of lymphoma cells with their microenvironment.Conclusion and clinical relevanceSelected candidate proteins with potential diagnostic value were evaluated on a tissue microarray (TMA). Primary lymphoma tissues of 126 different B cell‐derived lymphoma cases were included in the TMA analysis. The TMA analysis indicated gamma‐glutamyltranspeptidase 1 as a potential additional marker that can be included in a panel of markers for differential diagnosis of cHL versus NHL.