Distant metastases (DM) from childhood differentiated thyroid carcinoma (DTC) are uncommon and published studies are limited.To describe the outcomes of patients with DM from childhood DTC and to evaluate the molecular landscape of these tumors.Retrospective study at a tertiary cancer center including patients with pediatric DTC (diagnosed at age ≤18 years from 1946-2019) and DM.We identified 148 patients; 144 (97%) had papillary thyroid carcinoma (PTC) and 104 (70%) were female. Median age at DTC diagnosis was 13.4 (IQR 9.9-15.9) years. Evaluable subjects received a median of two (IQR 1-3) radioactive iodine (RAI) treatments at a median cumulative administered activity of 238.0 (IQR 147.5-351.0) mCi. The oncogenic driver was determined in 64/69 PTC samples: RET fusion (38/64; 59%), NTRK1/3 fusions (18/64; 28%), and the BRAF V600E mutation (8/64; 13%). At last evaluation, 93% had persistent disease. The median overall and disease-specific survival after DTC diagnosis were 50.7 and 52.8 years, respectively. Eight (5%) PTC patients died of disease after a median of 30.7 (IQR 20.6-37.6) years.Childhood DTC with DM persists in most patients despite multiple courses of RAI, but disease-specific death is uncommon, typically occurring decades after diagnosis. Fusion genes are highly prevalent in PTC and all identified molecular alterations have appropriate targeted therapies. Future studies should focus on expanding genotype-phenotype correlations, determining how to integrate molecularly-targeted therapy into treatment paradigms, and relying less on repeated courses of RAI to achieve cure in patients with DM from childhood DTC.