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A 63-yr-old-woman presented with pulmonary infiltrates and macroglobinemia. Open lung biopsy revealed an interstitial plasma cell infiltrate. Immunocytochemical staining to determine clonality of the infiltrate was negative for both kappa and lambda light chains and therefore was not helpful. Polymerase chain reaction (PCR) amplification of the CDR-III region of the immunoglobulin heavy chain gene revealed that the plasma cells were either monoclonal or biclonal, thus suggesting the diagnosis of a plasmacytoid pulmonary lymphoma. The advantages and limitations of the PCR technique over the traditional method of detecting gene rearrangements, i.e., restriction-digestion of DNA and Southern blotting, are discussed. To our knowledge this patient represents the first reported application of the PCR technique for detecting gene rearrangements to determine the clonality of a lymphoid infiltrate in the lung. This technique can also be applied to determine the clonality of lymphocytes obtained by bronchoalveolar lavage or needle biopsy, or from a pleural effusion.