An eight-year-old domestic shorthair cat was evaluated because of dyspnoea secondary to pleural effusion. Ultrasound examination identified a large anechoic cyst-like structure in the caudal thorax. A median sternotomy was performed, and the cystic mass was removed. Microscopically, the excised tissue was identified as a multilocular thyroglossal duct cyst with ectopic thyroid tissue. To the authors' knowledge, this is the first report of a mediastinal thyroglossal duct cyst in a cat. Despite the rarity of this lesion, it should be considered when a cystic thoracic structure is identified on thoracic ultrasound. Surgical excision of the cyst resulted in complete resolution of the pleural effusion and clinical signs.