Herein, we report on a lymphocytic hypophysitis related to a ruptured Rathke's cleft cyst which is not associated with pregnancy. A 45-year-old woman initially presented with headache and temporary double vision followed by amenorrhea. Preoperative imaging showed an intra- and suprasellar cystic mass. Complete resection of the tumor mass was performed via a transnasal, transseptal approach. Pathological examination displayed lymphocytic infiltrates within fibrotic tissue and residual pituitary cells accompanied by epithelial tissue of a Rathke's cleft cyst. The strongest inflammatory reaction was observed at the site of disrupture of the cyst integrity, suggesting that high protein levels from ruptured Rathke's cleft cyst might have triggered a lymphocytic hypophysitis. Our review of the literature provides further insights regarding the clinical behavior and different histological types of the lesions as well as the inflammatory changes that can occur in Rathke's cleft cysts.