Harlequin syndrome is rare and typically characterized by asymmetric flushing and sweating. Although it is usually considered idiopathic, literature review shows that it may be caused by lesion over lung apex or after central venous catheterization in the internal jugular vein. We present a 74-year-old woman who had been experiencing recurrent chest pain and right shoulder pain since 2 weeks ago. The tentative diagnosis was made by the emergency physician (EP) as acute coronary syndrome. The patient was given nitroglycerin treatment. Twelve hours later, the patient developed another episode of chest pain. The electrocardiogram and cardiac enzyme study results were, however, both normal. Further evaluation showed intermittent flushing over the left side of her face, as well as right-eye ptosis. A chest computed tomography (CT) was conducted, under the suspicion of Harlequin syndrome in combination with Horner syndrome, to derive the diagnosis of a right lung apex tumor. This case showed that history taking and physical examination are very important in the emergency department. It is particularly vital to observe the microchanges in the patient's symptoms and signs. It is also imperative to reassess the patient whose symptoms fail to improve under treatment, to look for other underlying lesions.