We present the clinical and histopathologic findings of a 38-year-old woman recently diagnosed with sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid (SMECE). This case is of particular interest because of its extremely aggressive clinical course. After total thyroidectomy, there was extensive bilateral thyroid lobe involvement with extension into perithyroidal soft tissues and the modified radical neck dissection contained 35 of 35 positive lymph nodes. This patient underwent 2 further surgeries; the first was a second right neck and supraclavicular surgery for lymph node metastases in which 8 of 11 were positive, followed a few months later by posterior neck surgery in which multiple lymph nodes were positive. Tumor was also documented by histological review from a right axillary lymph node. Imaging evidence of tumor in the lungs and liver was also present. Establishing the correct diagnosis of SMECE involves an awareness of the cyto- and histomorphologic features of this rare malignancy. As evidence that the biologic behavior of this neoplasm may well be more aggressive than previously considered, we briefly present the clinical and biologic course of this patient's neoplasm and a review of the literature.