Solitary peripheral nerve lymphomas are exceedingly rare primary manifestations of diffuse peripheral nervous system or central nervous system (CNS) lymphomatosis. A 52-year-old man presented with progressive weakness in gastrocnemius and anterior tibial muscle function, which was associated with radiating pain in the right leg. Magnetic resonance imaging studies revealed a solitary fusiform tumor, extending from the sciatic nerve, at the level of the lesser trochanter of the femur, into the posterior tibial nerve below the popliteal fossa. Intraoperative gross examination found that the tumor diffusely expanded the nerve, but did not extend from or into surrounding muscle or tendons. The final histological diagnosis was a solitary extranodal lymphoma (Burkittlike high-grade B-cell lymphoma). Postoperative staging did not reveal evidence of lymphomatous involvement of other organs, but additional chemo- and radiotherapies were administered. Four months after the surgical biopsy, the patient presented with a right facial nerve palsy. The results of cytological examination of cerebrospinal fluid were positive for the presence of atypical lymphocytes, which was consistent with apparently progressive neurolymphomatosis; however, the results of radiological studies were negative for systemic progression. The patient underwent intrathecal chemotherapy followed by systemic myelosuppressive chemotherapy with bone marrow rescue, but died of respiratory failure while still receiving treatment. Postmortem examination revealed extensive lymphomatosis in the peripheral nerves and spinal nerve roots without evidence of cranial nerve, CNS, or other organ system involvement. The aggressive biological characteristics of these tumors, their management, and pertinent literature are reviewed.