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Giant pituitary adenomas (GPAs) are defined as pituitary lesions larger than 40 mm of diameter. Surgical resection remains the gold standard to decompress the optic apparatus, reduce lesion load, and preserve hormonal function. The endoscopic endonasal approach (EEA) has been increasingly used for the treatment of pituitary adenomas and skull base tumors due to the wide angle of view and exposure. Through the description of an exemplificative case of EEA resection of a nonsecreting GPA in the setting of a multimodal treatment, the authors discuss the advantages and disadvantages of this management strategy and provide a detailed review of the literature.