A 59-year-old man treated with 5-fluorouracil and cisplatin for advanced oesophageal cancer presented abnormal behaviour and subsequently developed impairment of cognitive function, dysphagia and dysarthria on the fifth day of the treatment. Although brain computed tomography revealed no abnormal findings, brain magnetic resonance imaging using diffusion-weighted imaging clearly revealed the presence of a high signal intensity in the deep white matter of the bilateral cerebral hemispheres, including the corpus callosum symmetrically. A diagnosis of acute leukoencephalopathy was reached based on these findings. His clinical symptoms normalized four days after the discontinuation of the chemotherapy. Improvement in magnetic resonance imaging findings was delayed compared with that of clinical symptoms; however, the high signal intensity detected in the deep white matter had disappeared completely five months after the onset of symptoms. Early detection of drug-induced leukoencephalopathy is important as the clinical symptoms can be reversed by early discontinuation of the causative drug. Diffusion-weighted magnetic resonance imaging is a useful modality for the early detection and definitive diagnosis of this characteristic encephalopathy.