Intrathecal liposomal cytarabine (ITLC) has shown prolonged time to neurological deterioration in some patients with leptomeningeal spread of breast cancer. We describe a patient with fulminant chemical ventriculomeningitis leading to cerebral edema and death following ITLC administration. A 56-year-old Caucasian female developed progressive headache, depressed level of consciousness and adventitious movements immediately following ITLC. Neurological examination was normal prior to injection. This progressed to loss of all brainstem function and a head CT scan demonstrated diffuse cerebral edema. Due to the absence of neurological function on examination, the family opted to withdraw care. To our knowledge we report the first patient with fulminant chemical ventriculomeningitis leading to cerebral edema and death following ITLC administration. Adjunctive glucocorticoids are recommended. Treatment options are limited and complicated by the liposomal formulation of intrathecal cytarabine.