Thalidomide has found new uses as a tumor anti-angiogenesis agent that is capable of diminishing the proliferation of angiogenesis-dependent solid malignancies. Distantly metastatic, unresectable medullary thyroid carcinomas, as well as de-differentiated papillary and follicular thyroid carcinomas, which no longer concentrate radioiodine, have no known effective systemic therapies. We have verified, in the context of a completed phase 2 clinical trial, that thalidomide has significant activity in thyroid carcinomas that are no longer radioiodine avid and are rapidly progressive. This activity has only limited durability of around 7 months and is associated with significant toxicities of sedation, constipation and neuropathy.