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ABSTRACT: Objective: Malignant insulinoma is an extremely uncommon tumor that is usually accompanied by severe hypoglycemia that is difficult to manage. At this time, the long-term effect of 177Lu-DOTATATE (lutetium [Lu-177]-DOTA-Tyr3-octreotate) on this tumor is not well known. Methods: We report a case of severe, life-threatening, and refractory hypoglycemia associated with malignant insulinoma treated with 177Lu-DOTATATE. Results: A 51-year-old woman was referred because of severe, life-threatening, and refractory hypoglycemia due to malignant insulinoma. The patient had been treated unsuccessfully with chemotherapy, targeted therapies, and symptomatic therapy with diazoxide, steroids, and somatostatin analogues without success. 177Lu-DOTATATE adequately controlled her hypoglycemia after the other conventional treatments failed. Conclusion: 177Lu-DOTATATE was effective in providing rapid and long-term symptomatic control of the hypoglycemia and significantly improved the quality of life of the patient.