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Multiple sclerosis (MS) is a chronic demyelinating disease of a central nervous system. Neuropsychiatric symptoms are common in multiple sclerosis and bipolar disorder is one of the most common psychiatric disorders that coexist with MS. In this report, the association between bipolar disorder and MS is discussed through a case with an established diagnosis of MS and a manic episode with psychotic features. A 25-year-old female patient who has been followed up with the diagnosis of multiple sclerosis and has used beta-interferon for 2 years. She was treated with antidepressant medications when she was sixteen and had one manic episode induced by antidepressant medications, two other manic episodes and one hypomanic episode. She was admitted to our inpatient clinic with symptoms of hyperactivity, talkativeness, irritability, sleeplessness, suspiciousness and agitation. She had persecution and reference delusions. She was diagnosed to have “Bipolar disorder, manic episode with psychotic features” and Young Mania Rating Scale (YMRS) was rated as 31 point. Lithium 900 mg/day, olanzapine 20 mg/day, clonazepam 2 mg/day treatment was started. Clonazepam was discontinued gradually and lithium was titrated to 1200 mg/day. Other medications used by the patient were maintained. The symptoms were resolved. YMRS score decreased to 3. She was discharged with full remission on the 22th day of hospitalization. Bipolar disorder episodes like mania may be the first emerging symptom of MS as comorbid pathology or as an adverse effect of pharmacotherapies used in MS. The comorbidity of bipolar disorder and MS is well proven but its etiology is not known and has not been investigated precisely. Recent studies support a common genetic susceptibility. MS should be taken into account in differential diagnosis and excluded if a patient has both psychiatric symptoms and minor neurological findings. Management of bipolar disorder in MS is based on evidence provided by case reports and treatment should be individualized.