Objectives: We evaluated lymphosonography, or contrast-enhanced, ultrasonography (US)–guided sentinel lymph node (SLN) detection, as a technique for demonstrating the lymphatic drainage of the thyroid gland. Methods: In this prospective animal study, four 50-kg Yorkshire swine underwent transcutaneous injection of a US contrast agent and methylene blue dye into the thyroid gland. Contrast-enhanced US was used to identify draining lymphatic channels and SLNs. Sentinel node biopsy was conducted. Subsequently, bilateral neck and upper mediastinal dissection was carried out. Results: In 3 of 4 cases, a blue dye–positive and US contrast–positive SLN was identified. We identified SLNs in level IV in 2 cases. One case revealed 2 adjacent nodes in the superior mediastinum. In 1 case, a lymphatic channel was identified traveling into the mediastinum, but exposure of the SLN could not be obtained. No residual blue dye–positive or US contrast–positive nodes were identified on subsequent dissection. Conclusions: Lymphosonography of the thyroid gland in a porcine model correlates well with blue dye–guided sentinel node biopsy and is technically feasible, although in some cases access to the SLN may be difficult. This technique could potentially enable a detailed analysis of thyroidal lymphatic drainage if applied to humans.