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Background: Endoscopy is one of the initial diagnostic tests performed for the evaluation of upper gastrointestinal (GI) symptoms in clinical practice. Accurate interpretation and confirmation can be achieved by histopathological study of endoscopic biopsies and is one of the bases for planning proper treatment. Methods: Total 200 endoscopic biopsies, 50 from oesophagus, 50 from stomach and 100 from duodenum received in the department of pathology of a tertiary care medical college and hospital, Ahmedabad, Gujarat, India, over a period of two years from patients of all ages and sex with upper GI symptoms were included. Specimens were processed according to standard protocol and then reported by pathologist. The spectrum of histopathological lesions, whether inflammatory, non-neoplastic or neoplastic was evaluated along with the overall frequency, age and sex distribution of various upper gastrointestinal lesions. Result: Out of 200 cases of endoscopic biopsies received, 114 were males and 86 were females (M:F-1.3:1). Majority were non-neoplastic lesions comprising of 153 (76.5%) cases. Out of 38(19%) malignant cases, oesophagus was the most common site comprising 78.9% and duodenum was the least common site comprising 10.5% of total malignancy. In duodenum 25% cases of celiac disease were also identified. Conclusion: In this prospective study, the commonest site for upper GI endoscopic biopsy was from the duodenum (50%). Overall Inflammatory lesions were more common (76.5%), the predominant sites being stomach (88%) and duodenum (68%). Most common site for malignancy was oesophagus, histological type was Squamous Cell Carcinoma predominantly. Endoscopic biopsy serves as an effective tool for the diagnosis and management of upper gastrointestinal lesions.