Lymphomatosis cerebri is an atypical form of primary central nervous system lymphoma (PCNSL), which frequently causes rapid progression of dementia. A 68-year-old woman exhibited rapidly progressing disorientation and a mini-mental state examination score of 9. The fluid-attenuated inversion recovery of a magnetic resonance image (MRI) demonstrated focal areas of high-signal intensity in the right frontal lobe with a small enhancement, which was histologically diagnosed as diffuse large B-cell type lymphoma. The lesion dramatically shrank, and no enhancements were identified on MRI after treatment with high-dose methotrexate (MTX) and whole-brain radiation (WBR). However, her recovery of cognitive function was poor. The patient visited our clinic every 2 months but succumbed to systemic mycotic sepsis 14 months after the biopsy. Autopsy revealed lymphomatosis cerebri in the patient based on a feature of scattered small clusters of lymphoma cells infiltrating into the brain parenchyma in both cerebral hemispheres. Differentiation of lymphomatosis cerebri from other white matter degenerative diseases is usually challenging because lymphomatosis cerebri seldom forms mass lesions. In lymphomatosis cerebri, the lymphoma cells infiltrate into several regions in the brain tissue, including the basal ganglia, brainstem, and corpus callosum, in addition to periventricular and subcortical white matters. The rapid deterioration of cognitive function in the patient suggests a rapid spread of lymphomatosis cerebri, necessitating early histological diagnosis and prompt treatments. If the diagnosis is obtained, administration of high-dose MTX and WBR followed by rituximab and cytarabine can contribute to a longer survival time, based on our literature review.