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Symptomatic Rathke’s cleft cyst is usually accompanied by a long history of headache, visual disturbance, and hypopituitarism; however, rare cases present with acute onset and the clinical features in such cases remain uncertain. We report herein the clinical features of Rathke’s cleft cyst with acute onset and discuss the clinical significance. In this study, we defined acute onset as the clinical course with clinical symptoms within a 7-day history. From among 35 cases of symptomatic Rathke’s cleft cyst that were pathologically diagnosed at Fukuoka University Hospital between 1990 and 2009, five cases presented with acute onset. The symptoms, endocrinological findings, MR image findings, and pathological findings of these cases were analyzed retrospectively. Mean age was 56.8 years. Initial symptoms included headache (n = 3), general malaise (n = 2), polyuria (n = 2), and fever (n = 1). MR imaging revealed an intrasellar cystic lesion with suprasellar extension in all cases and showed rim enhancement in three cases. All cases were treated by transsphenoidal surgery. Pathological findings included hemorrhage (n = 2), hypophysitis (n = 2), and abscess formation in the cyst (n = 1). Postoperatively, all symptoms, except for hypopituitarism, improved in all cases. Rathke’s cleft cysts sometimes present with acute onset, and the presentation is consistent with the features of pituitary apoplexy caused by pituitary adenoma. Although pituitary apoplexy due to hemorrhage, inflammation, or infection due to an underlying Rathke’s cleft cyst is difficult to diagnose pre-operatively, Rathke’s cleft cyst should be included in the differential diagnosis, and early surgical treatment is needed, as for pituitary apoplexy caused by pituitary adenoma.