Neurosyphilis presentations can include psychiatric symptoms such as psychosis, mania, depression, or changes in personality. Therefore, it can lead to a misdiagnosis with psychiatric disorders. The diagnosis is particularly difficult in a subset of patients whose psychotic symptoms are developed as a manifestation of the disease later in life. With the aim to highlight the importance of considering neurosyphilis in the differential diagnosis of late psychosis, it is presented the clinical case of a from a Portuguese 69-year-old man, who presented symptoms of psychosis in the emergency room, ultimately diagnosed with neurosyphilis. A selective review of the literature was made using the database, with “neurosyphilis”, “psychosis”, “syphilis”, and “folie à deux” as keywords. Patient consent was obtained for the use of clinical data. Neurosyphilis represents the most severe consequence of an untreated syphilis infection and there is a need in the scientific community to establish tools to enhance the precision of diagnosis and treatment.Copyright © 2023, Alves et al.