We report a case of a 60-year-old woman with a history of intractable seizures and isolated delusional psychosis who was later diagnosed with steroid-responsive encephalopathy associated with autoimmune thyroiditis. The patient underwent right temporal lobectomy (epilepsy surgery) 15 years before coming to this clinic, but continued to have focal seizures, resulting in frequent emergency room visits thereafter. After admission for intensive inpatient video electroencephalogram monitoring and subsequent 7 months of close follow-up, both the electroencephalogram abnormalities and isolated delusional psychosis were found to be responsive to immunotherapy. This suggests that her epilepsy may be autoimmune in nature. Steroid-responsive encephalopathy associated with autoimmune thyroiditis was diagnosed after 26 years since the onset of seizures. Performing invasive epilepsy surgery in patients with autoimmune epilepsy cannot reverse the inflammatory process; therefore, it is reasonable to test for autoimmune etiologies before excision surgery on patients with medically intractable epilepsy. This case demonstrates the clinical use of quantitative electroencephalogram in assisting with the diagnosis of steroid-responsive encephalopathy associated with autoimmune thyroiditis and supports that it is a spectrum disorder with protean manifestations.