In patients with progressive metastatic (or recurrent) differentiated thyroid carcinoma that either do not take up radioiodine or are unresponsive to continued radioiodine therapy, staging is difficult and treatment options are few. However, in most of these patients uptake of radiolabeled somatostatin analogs is evident on somatostatin-receptor scintigraphy (SRS). Using SRS, patients with sufficient uptake of radiolabeled somatostatin analogs can be selected for high-dose peptide receptor radionuclide therapy (PRRT) as an alternative targeted-treatment option. PRRT with the beta-particle-emitting radionuclides (90)yttrium ((90)Y) and (177)lutetium ((177)Lu) gives the best results in terms of objective tumor response. Promising, novel, radiolabeled somatostatin analogs that have a broader receptor affinity profile and, thus, a potentially wider therapeutic range are being tested clinically.