Tyrosine kinase inhibitor is known to prolong progression free survival in radioiodine refractory thyroid cancer patients. Fatigue/asthenia/malaise is one of most common adverse events by the tyrosine kinase inhibitor treatment, and management of the adverse event is important to keep the drug medication longer which is essential for the survival benefit. In the case report, a radioiodine refractory thyroid cancer patient receiving tyrosine kinase inhibitor experienced severe fatigue, and a pathologic fracture of right humerus occurred by slipping down which was tightly linked with the adverse event of the drug. The pathologic fracture was surgically well managed and the adverse event was well controlled by supportive managements combined with dose reduction of the tyrosine kinase inhibitor. The drug administration to the patient was kept more than 1 year without progression of the disease.