Positive histological findings of a metastatic lymph node are often a guide to the detection of the primary lesion and can help clinicians in deciding appropriate therapeutic disciplines. We report on a case of a 64-year-old woman who presented with a lung tumor, a thyroid tumor and lymphadenopathy detected in a CT scan, and in whom we had difficulty interpreting the disease state. Biopsy of a supraclavicular lymph node demonstrated histological features of both papillary carcinoma and poorly differentiated adenocarcinoma. Transbronchial lung biopsy showed adenocarcinoma with signet-ring cells and fine needle aspiration of the thyroid tumor revealed papillary carcinoma. These findings made it difficult to determine the origin of each histological component, suggesting two possibilities; double cancer of the lung and thyroid, or transformation of papillary carcinoma into adenocarcinoma in the metastatic foci. Detection of activating epidermal growth factor receptor (EGFR) mutation in the adenocarcinoma samples obtained from the lung lesion motivated us to use erlotinib, a tyrosine kinase inhibitor, which was effective against the lung tumor and metastatic lymph nodes in the neck and the mediastinum. Total thyroidectomy and neck dissection following the targeted therapy a half year later revealed papillary carcinoma in the thyroid tumor without histological presentation of adenocarcinoma, and coexistence of adenocarcinoma and papillary carcinoma in seven lymph nodes. From these histological findings and the fact that the targeted therapy was effective against lung and lymph node lesions, we diagnosed that the adenocarcinoma originated from the lung tumor, not from transformation of the papillary carcinoma. One year after the surgery, no sign of recurrence has been observed for the thyroid lesion, and the patient is now receiving outpatient chemotherapy using bevacizumab and docetaxel.