We present a case of a 53-year-old HIV negative man with a 2-month history of progressive recent memory disturbance, gait disturbance and urinary incontinence. On MRI, an infiltrative tumor in the brain and spinal cord was noted. Subsequent positron emission tomography studies along with bone marrow biopsy and serum protein electrophoresis showed no evidence of systemic disease. Open brain biopsy results revealed a small lymphocytic infiltrate with scattered plasma cells in a predominantly perivascular growth pattern. The morphology was consistent with involvement by a low-grade B-cell lymphoma. Immunohistochemical findings showed CD20+, CD10-, CD5-, TdT-, EBV-encoded RNAin situ- and IgM- The above findings were consistent with involvement by a non-dural extranodal marginal zone B-cell lymphoma (MZBCL) primary to the brain and spinal cord. This is a case report of a CNS MZBCL of mucosa-associated lymphoid tissue type involving the brain and spinal cord parenchyma. © 2012 Japanese Society of Neuropathology.