Multiple sclerosis (MS) is an autoimmune disease that targets the myelin of the brain, spinal cord, and optic nerves. The inciting trigger that activates this immune response is unknown. Primary central nervous system (CNS) lymphoma is usually a diffuse large B-cell non-Hodgkin's lymphoma that originates in the brain, spinal cord, leptomeninges, or eyes. We report a 33-year-old patient who was diagnosed to have multiple sclerosis initially and a CNS lymphoma was noted 38 months later. Primary CNS lymphoma is a potential complication of chronic immunosuppression. Due to the uses of steroid, immunosuppresants and beta-interferon for multiple sclerosis, our patient developed an immuno-compromised state. These agents might contribute to the occurrence of a primary CNS lymphoma. On the other hand, a demyelinating disease may have preceded the diagnosis of primary CNS lymphoma. A possibility of neoplastic transformation in CNS inflammatory diseases such as multiple sclerosis may occur. The association of coexistent primary CNS lymphoma and multiple sclerosis may be more than coincidental.