Proper risk stratification of patients with differentiated thyroid cancer (DTC) is essential to avoid both unnecessary diagnostic procedures in low-risk patients and clinical inertia in cases that may require more aggressive treatment (1). One of the most widely used tools for prognostic stratification of patients with DTC is included in the American Thyroid Association (ATA) guidelines, which has been validated in several retrospective single-center studies (2) and developed on the basis of data from a literature review that included studies on different populations, settings and timeframes. In the prospective cohort study, we analyzed data from over 4000 cases of DTC managed in 40 different healthcare facilities in Italy. Our objectives were (i) to develop a comprehensive, data-driven predictive model capable of capturing the characteristics available at the time of initial treatment, (ii) to compare performance with the current ATA risk score and (iii) to determine the relative weight of various potential predictors.