Primary central nervous system (CNS) lymphomas are an uncommon form of brain neoplasm that should be considered in the immunocompromised patient with neurological changes. It can be difficult to distinguish primary CNS lymphoma from stroke on initial radiographic images. Neuroscience nurses who are involved in the care of these patients should be prepared to assist the patient and family in coping with an evolving diagnosis and in explaining the related diagnostic procedures, treatment options, and eventual discharge plan.