Over the past few years, the innovative field of magnifying endoscopy has been expanding with various cutting-edge technologies, one of which is endocytoscopy, to facilitate improvement in the detection and diagnosis of gastrointestinal lesions. Endocytoscopy is a novel ultra-high magnification endoscopic technique enabling high-quality in-vivo assessment of lesions found in the gastrointestinal tract with the use of intraprocedural stains. The main scope of this review article is to offer a closer look at the latest endocytoscopic technology and its clinical application in the upper gastrointestinal tract, especially in the esophagus and stomach, as well as to introduce readers to our simplified and up-to-date endocytoscopic classification, specifically developed for the esophagus and stomach, for the in-vivo assessment and diagnosis of esophageal and gastric lesions. Despite the good accuracy of endocytoscopy in the diagnosis of esophageal and gastric lesions in recent studies, some challenges still remain (e.g., staining method and standardized endocytoscopic classification). Through continuous evaluation and improvement of methods and skills, these challenges may be overcome thus establishing current techniques and classification, paving the way for further advances in the field of endocytoscopy and magnifying endoscopy. In all, endocytoscopy seems to aid in the in-vivo diagnosis of gastrointestinal tract lesions and may, in the future, revolutionize the field of in-vivo endoscopic diagnosis of gastrointestinal cancer, representing another step towards the so-called optical biopsy.