OBJECTIVE Older patients have a high prevalence of neurological and psychiatric disorders. They also have a baseline prevalence of late latent syphilis or positive syphilis serology. Thus the clinical question arises as to whether a neuropsychiatric disorder in a geriatric patient is neurosyphilis or if the positive serology is incidental. METHODS An illustrative case example is used to illustrate this dilemma. The relevant literature is reviewed. RESULTS The cerebrospinal fluid (CSF) protein is an important indicator of inflammatory activity in the central nervous system and is used as a clinical guide in the diagnosis. Elderly patients have higher values of normal CSF protein than younger patients. CONCLUSIONS Given the importance of CSF protein in the diagnosis of neurosyphilis, physicians must include this knowledge, that elderly patients have higher CSF protein values, in their clinical decision making in the differentiation between neurosyphilis and late latent syphilis in the elderly patient.