Lenvatinib is an oral multityrosine kinase inhibitor (TKI) with proven effectiveness in the treatment of radioactive iodine- (RAI-) refractory and/or unresectable differentiated thyroid carcinoma (DTC). The present study reports the case of a 41-year-old male who underwent hemithyroidectomy in June 2015 due to a thyroid nodule with fine-needle aspiration follicular neoplasm cytology and no evidence of malignancy in the histopathological exam. Three years later, acute disabling clinical symptoms emerged, mainly high skeletal pain conditioned with an important performance status decrease. PET/CT scan displayed several metastatic bone lesions in this context, located in the vertebral bodies, sternum, ribs, iliac crest, right acetabulum, and both necks of the femur. Histological study and immunohistochemistry confirmed DTC metastases, as they were strongly positive for thyroglobulin and TTF-1. At this point, the patient was unfit for conventional management that would have included completion of surgery and RAI treatment as first options. Thus, it was decided to start systemic treatment with TKI, Lenvatinib. Within the first week of treatment, the patient was almost asymptomatic and his performance status moved from 3 to 0. This allowed the patient to undergo resection of the thyroid gland remnant plus RAI treatment. Unfortunately, RAI refractory illness was confirmed so Lenvatinib treatment should be continued in this case until the evidence of no further clinical benefit. Despite drug adverse events, the patient continues with treatment one year later, remaining asymptomatic and with normal functional capacity.