Carmofur (1-hexylcarbamyl-5-fluorouracil), a derivative of 5-fluorouracil (5-FU), has been widely used in Japan as a postoperative adjuvant chemotherapy agent for colorectal and breast cancer. Periventricular hyperintensity on T2-weighted MR images in carmofur-induced leukoencephalopathy confront the physician with a broad range of differential diagnoses. We describe two cases of carmofur-induced leukoencephalopathy in which diffusion-weighted MR imaging revealed periventricular hyperintensity. We compared their findings with those of age-related periventricular hyperintensity in five patients and found discrepancies in signal intensity of periventricular areas. Our results suggest that diffusion-weighted MR imaging may be useful to differentiate carmofur-induced leukoencephalopathy from age-related periventricular hyperintensity.