BACKGROUND Non-islet cell tumor-induced hypoglycemia (NICTH), a major cause of fasting hypoglycemia, is caused by the overproduction of incompletely processed, high molecular-weight insulin-like growth factor-II (IGF-II), termed "big" IGF-II. To the best of our knowledge, only two cases of thyroid carcinoma associated with NICTH have been documented. METHODS We report the case of a 72-year-old woman who was brought to the emergency department with impaired consciousness. The patient had a history of pulmonary metastases from poorly differentiated thyroid carcinoma (PDTC), spanning 12 years since initial treatment. Laboratory tests showed decreased plasma glucose levels even though immunoreactive insulin, IGF-I, and growth hormone (GH) were undetectable. Computed tomography (CT) scan revealed macronodular pulmonary metastases the estimated volume of which was 456 mL. Both the biochemical data and imaging results suggested NICTH. The results of Western blot analysis performed on a fractionated serum sample showed an increased expression of big IGF-II, an important indicator in the diagnosis of NICTH. Because the massive pulmonary metastases were considered inoperable, immunohistochemical analysis of stored formalin-fixed, paraffin-embedded tissues was performed. The analysis revealed that the tumor cells were positive for both IGF-II and thyroglobulin. A whole-body CT excluded extrapulmonary metastatic lesions. A retrospective review revealed a gradual decrease in glycohemoglobin levels accompanied by an increase in the estimated volume of pulmonary metastases. These findings suggested that NICTH had been caused by pulmonary metastases from PDTC. CONCLUSIONS We describe here the third reported case of NICTH associated with thyroid carcinoma. This is also the first case reporting big IGF-II in the serum of a patient with thyroid carcinoma.