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Primary non-Hodgkin lymphoma arising at the site of metallic implant is very rare, and the possible carcinogenic effects of the metallic components and wear particles of the implant have not been answered despite many years of investigation. We report a case of large B-cell lymphoma occurring in a 78-year-old man who had a knee prosthesis implant for more than 30 years. The lymphoma was of microscopic size and found incidentally in the wear debris removed at surgical revision of the loosened prosthesis. The lymphoma expressed CD20, showed clonal rearrangements of immunoglobulin gene, and harbored Epstein-Barr virus (EBV). This case, together with previously reported cases, suggests that metallic implant-associated lymphoma is a distinctive subgroup of large B-cell lymphoma that shares many similarities with pyothorax-associated lymphoma and osteomyelitis-associated lymphoma, in that the lymphoma is an EBV-associated large B-cell lymphoma arising in a setting of chronic inflammation or irritation in a confined body space.