Multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy is characterized by asymmetric multifocal motor and sensory loss and conduction blocks in peripheral nerves. Peripheral demyelinating diseases may be accompanied by demyelination in the central nervous system (CNS). In this report, we present a patient with MADSAM who had a solitary tumefactive demyelinating lesion in the brain. Neuroimaging was performed because of a visual field defect revealed a right parietooccipital lesion, which was initially misdiagnosed as a tumor. A pathologic examination showed that it was demyelinating in nature. The patient developed peripheral nervous symptoms two years later and was then diagnosed as having MADSAM. There was a prominent clinical and electrophysiologic response to steroid treatment. Tumefactive brain involvement has not previously been reported for MADSAM neuropathy, although it has been documented in a single case of typical chronic inflammatory demyelinating polyneuropathy (CIDP). CNS involvement should therefore be considered in patients with MADSAM.