Lymphomatoid granulomatosis (LYG) is an angiocentric and angiodestructive lymphoproliferative disease involving extranodal sites. Although LYG cerebral lesions are usually located adjacent to LYG pulmonary lesions, few reports have described the occurrence of primary cerebral LYG. We herein discuss a case of a 40-year-old Japanese woman with primary cerebral LYG that caused various neurological symptoms for more than five years and progressed to methotrexate-associated lymphoproliferative disease under treatment with immunosuppressive therapy. This case suggests that primary cerebral LYG should be considered a lymphoid neoplasm manifesting as a primary brain tumor and a component of the differential diagnosis of chronic neuroinflammatory disorders.