A 33-year-old female is presented with the first case to our knowledge of new daily persistent headache (NDPH) with a large right benign non-toxic multinodular goiter causing carotid and vertebral compression with complete resolution of the headache immediately after thyroidectomy. Although this may be quite rare, hypothyroidism or hyperthyroidism causing NDPH, migraine, or an exacerbation of pre-existing migraine is not. Clinicians should consider routinely obtaining serum thyroid-stimulating hormone (TSH) and free T4 in patients with new onset frequent headaches or an exacerbation of prior primary headaches.