Material and Methods: Malignant pleural effusion in thyroid cancer is a very rare complication. We report an initial presentation of a differentiated papillary thyroid carcinoma with massive pleural effusion. A 79-year-old woman presented with a I-year history of an enlarging thyroid mass and dyspnea. A computed tomography scan of the chest showed a massive left-sided pleural effusion with complete collapse of the left lung, a biopsy of the thyroid mass was positive for papillary carcinoma. Pleural fluid cytology performed 3 times did not show any malignant cells. However, pleural fluid thyroglobulin level was 7356 ng/mL with the blood thyroglobulin level substantially lower at 1381 ng/mL with negative antibodies. The patient died 4 weeks after surgery from respiratory failure. Conclusion: We present a case of papillary thyroid cancer diagnosed after presenting with massive pleural effusion. Pleural involvement and effusion due to papillary thyroid cancer is rare and carries a very poor prognosis.