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Abstract Background Hashimoto’s encephalopathy (HE) is a rare but controversial syndrome showing a variety of neurological and psychiatric manifestations associated with autoimmune thyroiditis. Case presentation We present a case of 46-year-old hypertensive female who developed acute onset of behavioral symptoms mimicking affective disorder (mania). Investigations revealed high levels of anti-thyroid peroxidase antibodies with elevated thyroid-stimulating hormone. EEG and MRI findings were consistent with those seen in Hashimoto’s encephalopathy. She showed excellent response to high dose corticosteroids that helped in making the diagnosis of Hashimoto’s encephalopathy. Conclusions Hashimoto’s encephalopathy is an extremely important, though rare, diagnosis. It should be suspected and screened for in patients with encephalopathy of unknown origin because responses to treatment are usually excellent.