Abstract We correlated serial brain MRIs with neuropathological findings in a 16-year-old female whose autopsy was consistent with Wernicke's encephalopathy (WE). Diffusion-weighted imaging, diffusion coefficients mapping and neuropathology findings were suggested vasogenic edema in the periaqueductal and peri-the-fourth ventricular areas. This is the first documented case report to make this direct comparison. The characteristic WE changes in the mammillary body was also correlated with the findings of MRI with contrast enhancement. Bilateral cortical lesions revealed by MRI were atypical and rare in WE and were not evidenced by pathological changes.