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It was reported that BRAFV600E mutation correlates with radioactive iodine refractory papillary thyroid carcinoma (PTC) in local recurrence, whereas its relationship with 131I uptake status in distant metastatic PTC remains uncertain. This prospective study tried to explore the association between 131I uptake in distant metastases (DM) of PTC and BRAFV600E mutation status in their primary tumor.Seventy-three patients with DM were divided into BRAFV600E mutation group (n = 19) and wild-type BRAF group (n = 54) according to the BRAF mutation status. After posttherapy 131I whole-body scan was performed, the relation between 131I uptake in DM, BRAFV600E mutation status, and clinicopathological characteristics of 2 groups were compared.The mean age of mutation group was older than that of the wild-type group (P < 0.05). In the mutation group, 16 patients (84.2%, 16 of 19) were found to be with non–iodine-avid DM, whereas in wild-type group, only 5.6% (3 of 54) were with non–iodine-avid DM. The sensitivity and specificity of using BRAFV600E mutation for the identification of non–iodine-avid DM were 84.2% and 94.4%, respectively.BRAFV600E mutation in primary tumor might be a promising molecular marker to predict the status of 131I uptake in distal metastases.