We describe a patient with a clinical disorder that resembled vasculitic neuropathy in which peripheral nerves were successively affected over several months, but without systemic involvement. An initial muscle biopsy near the involved nerves showed signs of nonspecific inflammation around the muscle and nerve fibers. Immunosuppressive treatment resulted in a dramatic reduction in pain, but relapses of the disease eventually occurred, and the patient died 22 months after onset of the first symptoms. Pathologically, a malignant non-Hodgkin's B-cell lymphoma, restricted to the intra- and extradural peripheral nervous system, was found. The demonstration by Southern blotting of immunoglobulin heavy chain gene rearrangement confirmed the monoclonal nature of the lymphomatous cells. In situ hybridization tests for Epstein-Barr and herpes virus subtypes were negative. Our case underlines i) how difficult diagnosis can be despite extensive investigations, ii) the usefulness of immunosuppressive treatment in the early stage of the disease, iii) the importance of immunostaining and genome analysis for distinguishing between different types of human neurolymphomatosis, and iv) the fact that the initial inflammatory process in the muscle biopsy may be interpreted either as a paraneoplastic effect of the lymphoma or as a viral inflammatory neuromyopathy that triggers the development of the malignant lymphoma.