Leukoencephalopathy is progressive demyelination of the white matter, induced by a variety of factors. Among the causes of leukoencephalopathy, chemotherapy is an uncommon cause that generates potentially reversible lesions. The clinical presentation is classically made of alterations in mental status, hallucinations, hypertension, seizures, and acute visual changes. Imaging plays an important role in the diagnosis of this entity, especially by conventional and diffusion-weighted magnetic resonance imaging which enables an accurate diagnosis by identifying symmetric white matter lesions, especially in the parietal and occipital lobes. Herein, we report a 54-year-old female patient, newly diagnosed with non-metastatic moderately differentiated adenocarcinoma of the cecum. The patient received her first cancer chemotherapy (5-fluorouracil at 300 mg/m2). Five days later she was admitted to the intensive care unit for confusion following two generalized seizures. Conventional and diffusion-weighted magnetic resonance imaging was performed and showed diffuse white matter lesions of the parietal and occipital lobes. A diagnosis of 5-fluorouracil-induced leukoencephalopathy was established. The diagnosis of leukoencephalopathy should be considered in patients receiving cancer chemotherapy with alterations in mental status and seizures.