Key points: Due to its macrocyclic properties, lorlatinib has increased penetrance of the blood brain barrier compared to most other tyrosine kinase inhibitors.Lorlatinib is a promising therapy in patients with non‐small cell lung cancer with ALK or ROS1 rearrangements, particularly in patients with evidence of intracranial disease.However, behavioral and central nervous system side effects are common with lorlatinib.Lorlatinib can rarely result in severe psychosis, as with the presented case.In patients with lung cancer on lorlatinib, medication‐induced psychosis must be considered among the common differentials, including: the psychological response of patients to the cancer itself, somatic symptoms from brain metastases, and unmasking of underlying psychiatric disorders. [ABSTRACT FROM AUTHOR]