IntroductionThe sellar region and its boundaries represent a challenging area, harboring a variety of tissues of different linings. Therefore, a variety of diseases can arise or involve in this area (i.e., neoplastic or not). A total of three challenging cases of "chameleon" sellar lesions treated via EEA were described, and the lesions mimicked radiological features of common sellar masses such as craniopharyngiomas and/or pituitary adenomas, and we also report a literature review of similar cases. MethodsA retrospective analysis of three primary cases was conducted at the Università degli Studi di Napoli Federico II, Naples, Italy. Clinical information, radiological examinations, and pathology reports were illustrated. ResultsA total of three cases of so-called "chameleon" sellar lesions comprising two men and one woman were reported. Based on the intraoperative finding and pathological examination, we noticed that case 1 had suprasellar glioblastoma, case 2 had a primary neuroendocrine tumor, and case 3 had cavernous malformation. ConclusionNeurosurgeons should consider "unexpected" lesions of the sellar/suprasellar region in the preoperative differential diagnosis. A multidisciplinary approach with the collaboration of neurosurgeons, neuroradiologists, and pathologists plays a fundamental role. The recognition of unusual sellar lesions can help surgeons with better preoperative planning; so an endoscopic endonasal approach may represent a valid surgical technique to obtain decompression of the optic apparatus and vascular structures and finally a pathological diagnosis.