Purpose <p>To assess the clinical value of [¹⁸F]fluoroethyl-L-tyrosine PET ([¹⁸F]FET-PET) correlated with MRI in patients with functioning pituitary adenoma (FPA) with negative or equivocal conventional MRIs during diagnosis, persistent disease and recurrence.</p> Methods <p>Retrospective observational cohort study of 34 patients with FPAs who underwent a total of 37 [¹⁸F]FET-PETs (Cushing’s disease: <i>n</i> = 19, acromegaly: <i>n</i> = 14, prolactinoma: <i>n</i> = 3, and TSH producing adenoma: <i>n</i> = 1) between January 2022 and April 2025. The clinical performance was assessed in the surgically treated cohort, using confirmative histopathology and/or postoperative remission as reference standard.</p> Results <p>[¹⁸F]FET-PET identified a single lesion in 28 scans (76%), two lesions in 1 scan (3%), and no lesion in 8 scans (22%). [¹⁸F]FET-PET and MRI were concordant positive in 14/37 scans, concordant negative in 1/37, discordant MRI+/[¹⁸F]FET-PET + different location in 2/37, discordant MRI-/[¹⁸F]FET-PET + in 8/37, discordant MRI+/[¹⁸F]FET-PET- in 7/37 and partly concordant in 5/37 scans. In 14 cases surgery resulted in confirmative histopathology and/or postoperative remission, 12 of those had a positive [¹⁸F]FET-PET. In 6 cases surgery did not result in confirmative histopathology and/or postoperative remission, of whom 5 had a positive [¹⁸F]FET-PET. Overall, the sensitivity was 86% and the positive predictive value 71%. In three patients with acromegaly, [¹⁸F]FET-PET was able to localize a lesion, despite biochemical control under continued somatostatin analogue treatment.</p> Conclusion <p>[¹⁸F]FET-PET enhances lesion detection and improves personalized treatment in patients with FPA and negative or equivocal conventional MRIs throughout the disease course. Consensus on the timing of [¹⁸F]FET-PET with respect to medication and biochemical status is warranted.</p>