Primary sarcomas of the head and neck account for < 1% of tumors in this anatomic region. We present a case of a large anterior neck mass initially thought to originate from the thyroid gland but diagnosed as a cervical liposarcoma closely adjacent to the thyroid. A 64-year-old woman was referred for a right anterior neck mass that she first noticed about 6 weeks prior to evaluation. The patient reported mild degrees of dysphagia and dyspnea. Examination was notable for a large, painless, right anterolateral neck mass that was mobile on deglutition. Serum TSH level was unremarkable. Neck ultrasound revealed a well circumscribed 6.0 x 3.7 x 5.4 cm isoechoic mass that appeared to largely replace the right thyroid lobe. Fine needle biopsy yielded a specimen composed only of peripheral blood elements. Computed tomography of the neck revealed a 9.1 x 6.2 x 6.0 cm hypodense (- 4 Hounsfield units) mass originating in the right carotid space and displacing the trachea, larynx, and esophagus to the left of midline, the right sternocleidomastoid muscle anteriorly, and the right carotid artery and jugular vein laterally. Cytology on a core biopsy was notable for a pleomorphic spindle cell neoplasm with lipoid differentiation and positive staining for CD34 and vimentin felt to be consistent with a liposarcoma. The mass was removed during a right modified radical neck dissection, and postsurgical histopathology revealed an encapsulated tumor with negative surgical margins and MDM2 amplification by fluorescent in situ hybridization (FISH), making the final diagnosis a well-differentiated liposarcoma. Neck masses adjacent to the thyroid may appear to arise from thyroid parenchyma. Several tumors, including paragangliomas, very large parathyroid tumors, lipomas, and a case of low-grade fibromyxoid sarcoma are reported as mimicking thyroid nodules on initial evaluation. There is limited literature on liposarcomas of the head and neck, with 30 patients seen at M.D. Anderson from 1945-2005 the largest published case series. Well-differentiated liposarcomas accounted for approximately 25% (7/30) of cases, and painless neck mass as in this case was the most common presenting symptom. No patients with well-differentiated extrathyroidal liposarcomas died of their tumors in the M.D. Anderson series, in contrast to a tumor-related mortality rate of approximately 30% in the rare (N=13) cases of liposarcoma arising from the thyroid. A PubMed search failed to reveal any cases of liposarcoma mimicking a thyroid nodule. This case illustrates that large anterior neck masses require careful imaging evaluation to confirm apparent origin from the thyroid gland.