It has been reported that the thyroid is relatively immune to malignant metastasis. Therefore, in a practical setting, it is difficult to diagnose whether synchronous nodules in both lung and thyroid are independent or have metastasized from one to the other. In the present study, we report a treatment approach in a patient with such nodules, using a molecular technique. A 68-year-old woman presented with synchronous solitary thyroid mass and a nodular lesion in the right lung. Both tumors, which were surgically resected, morphologically showed neuroendocrine differentiation, which was confirmed by immunohistochemical analysis. These features required differential diagnosis from possible (1) medullary thyroid carcinoma (MTC) with metastasis to the lung, (2) pulmonary neuroendocrine carcinoma with metastasis to the thyroid, and (3) independent MTC and pulmonary neuroendocrine carcinoma. Identical mutations of the p53 gene were detected in both the thyroid and lung tumors, indicating the same origin for both tumors. In addition, these mutations and a lack of calcitonin expression suggested a pulmonary origin of the tumors. Metastatic thyroid cancers are well known to cause miliary lesions in the lung, while lung cancers can metastasize to various tissues. Furthermore, pulmonary neuroendocrine carcinoma has been reported as having a tendency of metastasizing to the thyroid. Head and neck surgeons should be aware that a particular subset of lung cancers may develop a metastatic solitary nodule in the thyroid, as presented. An effective therapeutic strategy is largely dependent on the differential diagnosis.