Background: Upper gastrointestinal tract disorders are one of the most commonly encountered problems in clinical practice. A variety of disorders can affect the upper GIT (gastro intestinal tract). The definitive diagnosis of upper gastrointestinal disorders rests on the histopathological confirmation and is one of the bases for planning proper treatment. Objectives: To determine the spectrum of histopathological lesions of upper gastrointestinal tract. To establish endoscopic biopsies as an effective tool in the proper diagnosis and management of various upper gastrointestinal tract lesions. Patients and Methods: A prospective study was conducted on the upper GIT endoscopic biopsies and the histopathological assessment was done at the department of pathology, M.S. Ramaiah medical college and teaching hospital from November 2006 to July 2008. Results: Of the total 25 cases of esophageal biopsies, 56% constituted non neoplastic lesions and 44% had neoplastic pathology. The most common malignancy was SCC (squamous cell carcinoma) occurred most commonly (73%) in the middle one third of the esophagus. In stomach biopsies, 41 (60%) had non neoplastic pathology and 27 patients (40%) had neoplastic pathology. The most common malignancy was adenocarcinoma. Conclusion: In our study, the commonest site for upper GI endoscopic biopsy was from the stomach (68%) with 60% non neoplastic and 40% neoplastic lesions. Most common neoplasm of the stomach was adenocarcinoma.. Out of the 100 cases, there was a consensus between endoscopic and histopathological diagnosis in 78% of the cases. Whenever there was a disagreement, the histopathological appearances served to correct a mistaken endoscopic finding. We therefore conclude that endoscopy is incomplete without biopsy and so the combination of methods provides a powerful diagnostic tool for better patient management.