Prostate-specific antigen (PSA) is the clinically most useful tumor marker for prostate cancer. Although false-positive elevations have been reported due to disease processes outside the prostate gland with the use of the polyclonal assay, such false-positive test results have been exceedingly rare with the use of the monoclonal assay. We report the case of a patient diagnosed with a B-cell lymphoma of the kidney and a significant elevation of serum PSA levels by monoclonal assay in the absence of either inflammatory or malignant prostate disease. PSA returned to normal during lymphoma-specific chemotherapy with a cyclophosphamide, mechlorethamine, vincristine, procarbazine, prednisone regimen. Possible explanations and clinical implications are discussed.