Two case histories, each spanning more than 20 years, demonstrate the complexity and persistence of modern neurosyphilis. Both patients present uncommon manifestations of neurosyphilis that may be easily overlooked today: superior orbital fissure syndrome, posterior fossa gumma, and bilateral deafness. Computed tomographic scans were performed in both patients but were diagnostically nonspecific, and syphilis serology testing in both serum and cerebrospinal fluid was repeatedly misleading. Numerous mistaken diagnoses were put forward until tissue was finally available for histologic examination. Perhaps the most disturbing aspects of these two cases are the persistent failure of specific treponemal serologic testing to indicate the diagnosis, and the inability of repeated “adequate” and/ or supramaximal doses of penicillin to prevent continued neurologic deterioration. We believe that chronic neurosyphilis may demand a reevaluation of current diagnostic and therapeutic practice