Background: Health economic appraisals often rely on the assessment of health utilities using preference-based measures (PBM). The cancer-specific PBM, European Organisation for Research and Treatment of Cancer Quality of Life Utility - Core 10 Dimensions (EORTC QLU-C10D), was developed recently, and now needs to be validated in various clinical populations. Methods: In a multicenter, multinational prospective cohort study, we longitudinally collected EORTC QLQ-C30 and EQ-5D-5L data from patients with thyroid cancer. We applied seven country-specific value sets to the QLQ-C30 data to derive country-specific utility values and used the EQ-5D-5L as a comparator PBM. Criterion validity was assessed by correlating index scores and Bland-Altman plots. Construct validity was investigated by correlating domain scores. Known-group comparisons and responsiveness were assessed using external clinical criteria. Results: A total of 181 patients with thyroid cancer from nine countries (three continents) provided analyzable data. Patients were included if they had differentiated, medullary, or anaplastic thyroid cancer. Mean utility values of both instruments were generally lower compared to general population norms. No floor or ceiling effects were present for the QLU-C10D. The intra-class correlation for EQ-5D-5L and QLU-C10D index values ranged from 0.761 to 0.901 across the measurement timepoints, supporting criterion validity. Spearman's correlation coefficients ranged from 0.289 to 0.716 for theoretically corresponding domain pairs. The QLU-C10D detected differences in 9 of 15 known-group comparisons, supporting sensitivity. Clinically important changes were detected by all QLU-C10D country specific value sets, supporting responsiveness. Further, the QLU-C10D had higher statistical efficiency than the EQ-5D-5L in 74.7% of comparisons. Conclusions: The QLU-C10D is a valid PBM for health economic evaluations in thyroid cancer studies. We recommend its use to estimate health utilities in economic evaluations of thyroid cancer therapies.