About 4000 people are diagnosed with thyroid carcinoma each year in France and as many as one in three adult patients have thyroid nodules on sonography. Nine in ten cases are differentiated (DTC). DTC may recur in the neck or metastasize very late, and final outcomes should therefore only be assessed after at least 20 years of follow-up. The goals of this study were to provide a reference for the evaluation of other protocols, to evaluate the benefits and risks of radioiodine, and to identify the most effective management option. We examined 25-year outcomes in a series of 850 DTC patients who were operated on and monitored with the same protocols. We used an original classification (Ext-Tg) that includes both the initial extension and the thyroglobulin (Tg) level at the end of initial treatment. The low-risk group, composed of patients with Tg <10 microg/l after ablation of thyroid remnants, included patients at stage 1 (microcarcinoma, n=268), stage 2 (intra-thyroidal carcinoma, n=310), and stage 3 (DTC with node invasion, n=142). Stage 4 disease consisted of DTC with some non excisable tumor in the neck, and/or metastasis, and/or stimulated Tg >10 microg/l after remnant ablation. Most patients had total thyroidectomy followed by radioiodine ablation, periodic monitoring adapted to the stage, and suppressive therapy. At 25 years the actuarial rates of cancer-related death among patients with initial stage 1, 2, 3 and 4 disease were respectively 0%, 1,4%, 0% and 46,9%. The overall recurrence rates were respectively 3,6%, 3,8%, 5,3% and 44,5%. The rates of cervical recurrence necessitating surgery were 3,8%, 2,4%, 3,4% and 23,7%. Serious complications of treatment, including radioiodine, were rare. We conclude that:--good long-term results are more likely to be obtained when total thyroidectomy and radioiodine are combined with an early detection of recurrences (before they are visible by traditional imaging methods);--patients must be strictly staged in order to guide the modalities and duration of follow-up, and the Ext-TG classification seems more appropriate than all those which do not consider the Tg level at the end of initial treatment;--in experienced hands the benefits of total surgical ablation of the tumor greatly outweigh the potential risks;--radioiodine is effective and safe when appropriate measures are taken to prevent complications, and the long-term eficacy of surveillance without total body scanning should be verified before being universally adopted;--cost-reduction should focus on diagnosis, screening, and the selection of nodules eligible for surgery, rather than on monitoring of patients with DTC. DTC is thus a paradigm of a disease in which it is possible to optimize the long-term results and to lower costs by monitoring small and non-suspect nodules.