: Wernicke encephalopathy (WE) is an acute or subacute neurologic disorder resulting from thiamine deficiency. A Magnetic Resonance Imaging (MRI) test is useful in addition to the clinical manifestation, which is the main basis for the diagnosis. Typical MRI findings include areas surrounding the aqueduct and third ventricle, as well as those in the medial thalamus, dorsal medulla, tectal plate, and mamillary bodies. We reported a case of WE with extensive cortical lesions. The beneficial effects of thiamine supplementation and low dosage of glucocorticoid did not sustain after discharge. Eventually, we found that the condition he had was brought on by gastric diffuse large B-cell lymphoma. Thiamine supplements combined with glucocorticoids may be a good administration regimen. The etiology of WE is frequently disregarded. In individuals with WE, it is essential to take the underlying illness into account. Malignancy, especially gastrointestinal tract cancer, should be considered. A good administration regimen may include glucocorticoids and thiamine supplements.