Once an extremely rare neoplasm, primary lymphoma of the central nervous system (CNS) now ranks behind only meningiomas and low-grade astrocytomas in prevalence. Understanding of primary CNS lymphoma has increased greatly in recent years as a result of special immunohistochemical stains. Virtually all primary CNS lymphomas are composed of B cells. Although a viral cause has been suggested in some cases, the exact cause of the disease is still under investigation. Primary CNS lymphoma has a distinct affinity for perivascular extension. Although granular nodules may be seen at gross pathologic inspection, diffuse microscopic spread is always present, which accounts for the ability of this tumor to produce distant disease and local recurrences. The dense cellularity of the tumor and its predilection for the periventricular region also explains its typical hyperattenuated appearance on unenhanced computed tomographic scans and hypointensity on T2-weighted magnetic resonance images. Virtually all lesions enhance with contrast material. Although the overall prognosis for patients with primary CNS lymphoma remains poor, some advances have been made with radiation therapy and chemotherapy for this once uniformly fatal disease.