Objective: To evaluate and compare staging systems for differentiated thyroid carcinoma and predicted outcome in an endemic goiter region with iodine substitution and to examine the risk profile of differentiated thyroid carcinoma and compare it against nongoiter regions., Summary Background Data: Differentiated (papillary or follicular) thyroid carcinoma has a favorable prognostic outcome. In numerous studies prognostic factors have been identified and staging systems created, particularly in Anglo-American centers (nonendemic goiter regions), to evaluate individual prognostic outcome., Methods: In a retrospective study, the authors assessed 440 patients with differentiated thyroid carcinoma (papillary, n = 293; follicular, n = 147) and a long-term follow-up of median 10.6 years to determine the predictive accuracy of nine staging systems applicable to the study population; the systems were compared by calculating the proportion of variation explained., Results: With regard to cause-specific mortality, the difference between the respective stages and/or risk groups was highly significant for every staging system. By means of calculating the proportion of variation explained, MACIS scoring supplied the most reliable prognostic information for differentiated thyroid carcinoma (relative importance 16.93%). EORTC and UICC/AJCC systems had a relative importance of 16.34% and 13.96%, respectively, also a high level of accuracy; this implies that they are superior to the other six staging systems. If we separate papillary and follicular carcinoma, for the former the MACIS score with a relative importance of 15.05% is clearly superior to the other staging systems, whereas for the latter the EORTC score and the UICC/AJCC staging system, with relative importance of 17.04% and 16.58%, respectively, yield the best prognostic information., Conclusions: By applying staging systems in an endemic goiter region with iodine substitution, the best prognostic information for papillary thyroid carcinoma has been achieved with the MACIS score, while for follicular thyroid carcinoma the EORTC score and the UICC/AJCC system have the best prognostic accuracy. Because of the individual factors, which are easy to obtain and generally available (age, T, N, M classification), the uncomplicated handling, and the widespread use and the good predictive accuracy, the UICC/AJCC classification is the staging system of choice for comparing published results.