Introduction. Cushing’s disease (CD) represents 10—12% of all pituitary adenomas and is seen predominantly in women, with a female-to-male ratio of 8:1. Although most patients with ACTH-secreting adenomas present with benign, small tumors, some have invasive macroadenomas. Rarely, nonfunctional pituitary adenomas (NFPAs) may gain secretory function, but there have been a few case reports of metamorphosis to CD. Case report. We report the case of a 59-year-old female diagnosed in 2007 with a NFPA and panhypopituitarism. She had two transsphenoidal surgeries and Gamma Knife therapy and started replacement treatment with levothyroxine 75 mcg/day and prednisone 5 mg/day. The postoperative course was favorable and imagistic follow-up between 2007—2014 showed progressive reduction of the residual tumor and empty sella. From personal history we note noninsulin-dependent diabetes mellitus, postmenopausal osteoporosis treated with bisphosphonates. In January 2015 she suffered visual loss on the right eye. Pituitary MRI showed supra and parasellar tumor recurrence of 27/24/17 mm, infiltrating the right side of the cavernous sinus, extending around the right internal carotid artery and optic nerve, compressing the optic chiasm. In March 2015 a third transsphenoidal partial excision of the tumor was performed and in August Gamma Knife therapy was repeated. The histopathological examination was consistent with a pituitary adenoma but immunohistochemical staining for ACTH was positive, with Ki-67 25%. She had no non-specific cushingoid features. Laboratory test: glucose 116 mg/dl, HbA1c 7.5%, FSH 3.34 mIU/ml, LH 0.585 mIU/ml TSH 0.044 mcIU/ml, FT4 1.13 ng/dl. Prednisone replacement therapy was stopped and CD was confirmed: 8 AMcortisol 13.3 mcg/dl, 23 PMcortisol 11.3 mcg/dl, ACTH 70.2 pg/ml, 8 AMcortisol after 1 mg dexamethasone overnight 13.8 mcg/dl. Ophthalmic exam: blindness in the right eye, slightly decreased visual field in the left eye. Pituitary MRI 8-month postsurgery revealed a 28/31/28 mm invasive tumor. We started treatment with Cabergoline 3 mg/week and recommended closely biological and imagistic follow-up, hoping for a good response to radiotherapy. Conclusions. Our case stresses the importance of regular, lifelong follow-up of patients with NFPAs. Chiloiro et al have reported that pituitary adenomas with Ki-67 ≥1.5% have a higher risk of recurrence. Although the characteristics of patients with CD have been well known for decades, the diagnosis and management of this disease are often challenging.