A 45-year-old woman, with a history of asymmetric facial flushing, was presented to the Endocrinology Unit after pituitary macroadenoma removal. After other pathological entities had been ruled out, she was diagnosed with harlequin syndrome following a lesion of the postganglionic sympathetic fibers during transsphenoidal pituitary macroadenoma surgery. We herein report the first case of harlequin syndrome following transsphenoidal pituitary surgery. We describe this difficult and benign diagnosis along with its characteristic imaging.