As we all know there has been a recent resurgence in the incidence of syphilis worldwide. Presented here is a case report of a 46 year old African- American male with no past psychiatric history, who presented with an acute onset of psychotic symptoms including delusions, hallucinations and aggressiveness. The patient was later diagnosed as having Neurosyphilis at a large community hospital and was started on benzathine penicillin G, 2.4 million units I/M every week for 3 weeks, and was later transferred to a state mental hospital to treat his psychosis. Patient was then tried on quetiapine with the target bid dose of 400mg (am) and 600mg (pm) along with benztropine 2mg tid. After 3 weeks, the patient’s hallucinations and aggressiveness improved, his EPS also became better. One of the objectives of this case report is to compare the patient’s response to different trials of antipsychotics and to also emphasize the importance of routine screening for syphilis as part of the diagnostic work up of psychosis.