Primary lymphoma of the thyroid gland is rare. The histopathology of most low-grade thyroid lymphomas is of a mucosa-associated lymphoid tissue (MALT) type. A typical feature of this type of lymphoma is a close lymphocyte-epithelium interaction. It tends to appear in patients with a history of autoimmune disease or chronic inflammatory disorders. A clinical picture of hypothyroidism may be present. Hyperthyroidism associated with thyroid lymphoma is also rare. Thyroid lymphoma could be misdiagnosed as lymphocytic thyroiditis or small cell anaplastic carcinoma. It is rarely reported in patients with Down's syndrome. In this report, we describe a Down's syndrome patient with MALT thyroid lymphoma and cerebral infarction. The patient, a 42-year-old man, presented with chest discomfort and bilateral leg weakness of one week's duration. Physical examination of his neck showed a right-sided mass lesion. Neurologic examination revealed decreased muscle power and hyperreflexia in both lower legs. Babinski's sign was present bilaterally. Endocrinologic studies showed subclinical hypothyroidism. A thoracolumbar radiograph showed disc space narrowing. Thyroid sonography revealed a hypoechoic mass lesion in the right lobe of the thyroid gland. Fine needle aspiration cytology of the neck mass demonstrated a large amount of lymphocyte infiltration. An I131 thyroid scan and 24-hour uptake revealed the possibility of thyroid malignancy at the upper poles of both thyroid lobes. Computerized tomography of the brain revealed a lacunar infarct in the posterior aspect of the left putamen. Magnetic resonance imaging of the lumbar spine revealed a healed L4 compression fracture with L4-5 retrolithesis. The patient later underwent a right total thyroidectomy. The pathologic finding showed MALT lymphoma. The patient received steroid suppression therapy, and after nine months of treatment and follow-up, he developed clinical hypothyroidism. Neither local tumor recurrence nor distant metastasis was found.