Acute lymphoblastic leukemia (ALL) accounts for 80% of childhood leukemia cases. It is common between 3 and 7 years of age. Organic brain syndrome is a clinical syndrome that progresses with impaired consciousness as well as memory, perception, orientation, behavior and sleep rhythm disorders. It is common among patients admitted to hospital. Etiology includes infections, metabolic causes, endocrine causes, cancers, and drugs. A 14-year-old girl, who was admitted to pediatric hematology clinic with a diagnosis of ALL, was consulted due to mood disorder developed during chemotherapy. Abnormal ideas, ridiculous talks, and forgetfulness had begun in the patient with no previous complaint. She had had skepticism, and had mentioned that some nurses would kill her and occasionally showed coffins to her. The patient had displayed resistance during therapy. She had been mentioning that she speaks with God and all praying and thoughts are realized. There was no event or head trauma that may be a potential cause, and there was no history of such events. When drugs used were questioned, it was found that she received third dose of intrathecal methotrexate treatment a few days before symptom onset. The patient was consulted to neurology department and no pathology other than the existing picture was detected on cranial MR imaging or EEG. The patient was diagnosed as having organic brain syndrome with detailed history taking. It was observed that there were increased and scattered associations and that she was euphoric. Initially, haloperidol (5 mg/day) and biperiden (1 mg/day) were prescribed to the patient. Haloperidol was titrated to 10 mg/day due to persisting skepticism and inappropriate affection. Biperiden dose was escalated to 2 mg/day due to development of EPS. Currently, the patient is attending control visits and receiving treatment for ALL, who had resolution in psychiatric complaints. Organic brain syndrome is second most commonly encountered psychiatric diagnosis in cancer patients admitted to hospital with a frequency of 14-55%. Delirium is an irreversible condition either associated with the treatment or occurring spontaneously, which has an acute onset. Delirium emerges with mood alterations and auditory and visual hallucinations, changes in sleep and wakefulness patterns, disorientation, incoherent thoughts, psychomotor agitation or retardation, irritability, aggressiveness, difficulty to concentrate, difficulty in verbalism or inability to recall are early signs. Primary or metastatic brain tumors can cause delirium or other neurological symptoms by compressing cerebral vasculature or blocking şow of cerebrovascular cerebrospinal mı? şuid (CSF). Encephalopathy can be observed following cranial radiotherapy and it may onset within first hours of therapy, persisting weeks to years. Interleukin-2 and interferon-α can cause acute confusion or other disorders such as depression and mania. There are three primary goals in the treatment of delirium. These include resolving factors leading delirium, ensuring patient’s safety while providing education to patients, parents, and caregivers and providing symptomatic treatment for behavioral disorders related to delirium. In our case, medical therapy was prescribed to the patient; information was provided to parents and healthcare providers, and patient was placed in a secure and silent room, emphasizing value of these measures in resolution.