Differentiated thyroid cancer (DTC), including papillary and follicular carcinoma with histological variants, has an excellent prognosis; nevertheless a subset of these tumours is clinically aggressive and, in some patients, fatal. Treatment of DTC remains controversial, regarding the extent of primary surgical resection, the need for lymph node dissection and the role of postoperative radioactive iodine ablation. In addition to the widely accepted TNM classification, recognition of significant risk factors and developing of staging systems, such as AMES, AGES, MACIS, MSKCC and NTCTCS, has helped to identify the patients with a potential aggressive course of the disease and high risk of recurrence. This has allowed the development of a rational and selective approach to therapy, thus, avoiding excessive treatment and subsequent morbidity without compromising the oncological outcome.