Acute suppurative thyroiditis is a very uncommon disorder, most often arising in children with congenital conditions connecting the thyroid directly to the oropharynx, such as a piriform fistula or thyroglossal duct. Accordingly, the most common causative agents are those which can colonize the oral mucosa and spread to the thyroid contiguously, such as Streptococcus species, Staphylococcus species and anerobes. In adults, a hematogenous spread to a pre-existing altered thyroid gland is often the postulated pathogenetic mechanism, and it is exceedingly rare in the United States. We report the case of an 81-yr-old woman with acute suppurative thyroiditis secondary to Escherichia coli (E. coli) infection. The patient presented with fevers, chills, dysuria and recent painful neck swelling. Thyroid ultrasound and neck computed tomography revealed a multinodular goiter and an intra-thyroid abscess. An otolaryngology evaluation and barium swallow failed to show a piriform fistula. Thyroid hormone levels were consistent with hyperthyroidism. Urine cultures were positive for E. coli. The patient subsequently developed a clinical picture consistent with severe thyrotoxicosis, which rapidly resolved after medical treatment, appropriate antibiotics and surgical drainage of the thyroid. Abscess material also grew E. coli. Thus, acute suppurative thyroiditis secondary to sepsis can complicate an otherwise asymptomatic multinodular goiter and should be promptly treated with broad-spectrum antibiotics and/or surgical drainage to avoid serious consequences, including severe thyrotoxicosis.