BACKGROUND This report describes two cases with unexplained positive results for phencyclidine (PCP). OBJECTIVE This case will correlate lamotrigine (Lamictal®) use with false-positive results for PCP on a rapid urine toxicology screen. METHODS Case 1: A 62-year-old male arrived to the emergency department in extreme psychosis. All positive results on the urine drug screen could be accounted for except PCP. A comprehensive drug screen was performed to confirm PCP use, but returned negative. PCP was ruled out as the causative agent. The reason for the PCP false positive remained unknown. Case 2: A 49-year-old female presented to the ED with a history of seizures and depression. Despite positive PCP results on a rapid urine drug screen, PCP use was ruled out due to patient presentation and comprehensive history. RESULTS The differential diagnosis in case 1 included PCP abuse until PCP was ruled out by a comprehensive drug screen. A literature search failed to explain a reason for false-positive results. The patient in case 2 was not psychotic, but returned a positive urinalysis result for PCP. Case 2's presentation combined with a comprehensive history at the facility ruled out PCP use. Both patients were taking the anti-seizure medication lamotrigine with nothing else in common. CONCLUSIONS Lamotrigine has the potential to cause false-positive results for PCP on the Bio-Rad TOX/See urine toxicology screen.