We present the case of a male patient, initially treated for myxedema coma secondary to Hashimoto's thyroiditis, who was discharged on levothyroxine and a low-dose steroid taper but was re-admitted for the treatment of status epilepticus. During the second admission, the patient developed encephalopathy and cognitive dysfunction. Thyroid peroxidase (TPO) antibodies (Abs) were elevated and the patient was treated with high-dose steroids with clinical improvement. The patient was determined to have Hashimoto's encephalopathy (HE) due to the clinical picture as well as the response to high-dose glucocorticoid therapy. Cerebrospinal fluid (CSF) analysis demonstrated elevated protein, immunoglobulin G (IgG) index, and IgG synthesis rate; however, albumin index was elevated, indicating a disrupted blood-brain barrier. We suggest that HE be considered in the differential diagnosis for patients presenting with seizures, coma, stroke-like symptoms, behavior changes, and unexplained encephalopathy. After ruling out more common pathologies, HE should be considered by testing for anti-TPO Abs.