Metastatic follicular thyroid carcinoma (FTC), unresectable or resistance to radioactive iodine, is associated with poor survival. It is believed that this kind of FTC is driven by mutated genes. However, what kind of changes of genome and underlying mechanisms are elusive. The aim of this article is to understand whether there are somatic mutations in circulating cell-free tumor DNA (cfDNA) in a FTC patient with lung and bone metastases. A 55-year-old woman was diagnosed with FTC with bone and lung metastases. Appropriate amounts of DNA were extracted from formalin-fixed, paraffin-embedded thyroid tumor, peripheral cell-free plasma, and peripheral blood leukocytes and then sequenced. The significance of DNA sequencing was evaluated. There were 13,519 common variants in both tissue DNA and cfDNA. Fifty-five somatic mutations were identified in tumor, with 5 of them nonsynonymous. Seventy-two somatic mutations were found in cfDNA, with 2 of them causing amino acid change. Sixteen common alterations existed in both samples, that is, 31.3% of all the tissue somatic mutations. This pilot study provided proof that cfDNA represents the genomic characteristics of FTC primary tissue DNA well, but also metastatic tumors. Further studies are needed to better prove the effectiveness of cfDNA in the field of thyroid cancer metastatic mechanism research and real-time monitoring.