In attempting to identify antigens that are differentially expressed on tumor cells following transformation from follicular small cleaved cell lymphoma (FSC) to immunoblastic lymphoma (IL), we identified a unique epitope of the transferrin receptor (TfR). The epitope is available for binding in aggressive lymphomas but not in indolent lymphomas or normal cells. An immunoglobulin G2a (IgG2a) antibody that binds this epitope, Trump, was produced by screening on tumor cells from a patient who initially had a low-grade lymphoma which subsequently converted to a high-grade lymphoma. Immunoprecipitation and comodulation studies show that Trump binds to the TfR, but blocking studies and immunostaining reveal that the TfR epitope seen by Trump is distinct from the OKT9 and anti-TfR binding sites. The ability of Trump to discriminate a separate population of more highly malignant cells suggests that the expression of the Trump epitope is determined by the state of activation or degree of malignancy of the cell. In addition, it may be possible to use the Trump antibody diagnostically or therapeutically in the management of lymphomas.