Differentiated thyroid carcinoma (DTC), including papillary and follicular thyroid carcinomas, is usually curable when diagnosed at an early stage. Nevertheless, the management of DTC is multidisciplinary and remains highly controversial. There is still no worldwide consensus regarding the appropriate degree of surgical resection or when and how much radioiodine should be given. Generally, surgeons remove the appropriate thyroid tissue and the involved lymph nodes. Pathologists evaluate the cell type and aggressiveness of the tumor and the nodal involvement. In patients with a high risk of recurrence or metastasis, the residual thyroid tissue is ablated with iodine-131. A high level of serum thyroid-stimulating hormone (TSH) is required in patients to ensure an appropriate therapeutic response, which can be achieved by thyroxine withdrawal 6–8 weeks after surgery or by the administration of recombinant human TSH two days before 131I treatment. A post-ablation 131I whole-body scan (WBS) is mandatory to evaluate the patient’s DTC status. Suppressive thyroxine treatment to maintain serum TSH values below or in the lower normal range and follow-up 131I WBS in conjunction with measurements of serum thyroglobulin (Tg) are usually necessary to prevent or detect tumor relapse or spread. Correlations are made with other imaging modalities and with clinical findings, to ensure there is no evidence of disease and to provide optimal patient care. Cumulative data indicate that adjunctive 131I treatment in patients with DTC can reduce recurrence rates and improve survival rates for patients older than 40 years.