This 52-year-old male without a significant medical history was receiving chemotherapy with diethylnorspermine (DENSPM), a polyamine analogue, for a partially resected pancreatic adenocarcinoma. Ten months after his initial diagnosis, he was admitted to an outside hospital for evaluation of altered mental status. Over the course of the next few days the patient developed progressive neurologic signs and symptoms including lethargy, tonic deviation of his eyes to the left, asymmetic pupils, and right-sided decerebrate posturing elicited by painful stimuli. Neuroimaging studies revealed multiple lesions scattered in the periventricular white matter, thalamus, midbrain pons, and cerebellar peduncles. The clinical and neuroimaging differential diagnoses are discussed, and postmortem neuropathologic correlation is presented.