A patient with a localized HTLV-I-associated lymphoproliferative disease that was misdiagnosed as Hodgkin's disease is presented. The patient's serum was negative for HTLV-I antibodies by enzyme-linked immunosorbent assay (ELISA), Western blot, and radioimmunoprecipitation. Tumor tissue DNA was negative for HTLV-I by Southern blotting but was positive for distinct HTLV-I sequences when subjected to DNA amplification using the polymerase chain reaction. We conclude that the clinical and pathologic diagnosis of HTLV-I-related lymphoma can be difficult and can be confused with Hodgkin's disease. Extremely sensitive molecular biological techniques may be required to establish a diagnosis of HTLV-I-induced lymphoma.