This chapter discusses rare and rapidly progressive syndromes with neurocognitive manifestations. Due to their rapid course, these syndromes are more often encountered in the inpatient setting but are subject to misdiagnosis due to their rarity. Thorough work-up and early identification are important to rule out more common diagnostic differentials such as gradually progressive neurodegenerative diseases or acute delirium. In inpatient settings, opportunities to conduct extended cognitive evaluation are limited. Emphasis on thorough clinical history and high-yield clinical signs is key, yet clinicians must also be wary of undue false positives. The inpatient neuropsychologist can play a critical role in identifying neurobehavioral patterns that aid in diagnosis, management, and treatment of these patients.