Hand-foot syndrome (HFS) is a common adverse event associated with lenvatinib treatment. Lenvatinib dose adjustment using therapeutic drug monitoring may be beneficial in the management of HFS, as symptoms improve with dose reduction or treatment interruption. The serum lenvatinib levels were monitored in a patient with lenvatinib-induced HFS. A 74-year-old woman was administered lenvatinib (24 mg/d) for papillary thyroid cancer. Although lenvatinib was withheld several times owing to the occurrence of HFS, the severity of the HFS was controlled to within grade 1 by reducing the dose to 4 mg/d. The lenvatinib dose was subsequently increased to 8 mg/d owing to the progression of lung metastases, resulting in increased HFS severity. The association between serum lenvatinib levels and the severity of HFS was examined in this case: serum lenvatinib levels were higher in grade 2 HFS than in grade 1 HFS (median 42.1 vs. 22.5 ng/mL; P < 0.05). This case's findings suggest that serum lenvatinib concentrations are associated with the severity of lenvatinib-induced HFS and that there may be an overlap between drug concentrations, metastatic suppression, and the grade of HFS.