Abstract Introduction We report what is to the best of our knowledge the second adult case of chylothorax clearly associated with severe hypothyroidism in the English-language medical literature. To the best of our knowledge, this is the first case of its kind reported without a prior history of malignancy. Case presentation A 37-year-old Hispanic woman with no reported significant past medical history initially presented with shortness of breath and inability to lose weight. She was found to have a large chylous effusion requiring chest-tube drainage, as well as severe hypothyroidism. After several weeks of thyroid hormone-replacement therapy, the formation of chylous pleural fluid in the patient greatly diminished, and the chest tube was removed. Upon long-term follow-up her minimal residual effusion remains stable on serial chest radiographs. Conclusion Although the exact pathophysiologic relation between low thyroid hormone levels and chyle formation remains to be elucidated, hypothyroidism should be a diagnostic consideration in patients with chylous effusions, especially those refractory to conventional treatments.