Objectives: To assess the histopathological spectrum of upper gastrointestinal biopsies among patients with various upper GI symptoms and their association with H. pylori, alcohol and smoking. Material and method: The present study was a cross-sectional study, carried out on patients of Ispat General Hospital from December 2014 to Nov 2015. Endoscopic biopsy was taken and followed by histopathological evaluation. Results: Out of total 100 biopsies, 64 were gastric biopsies, 20 duodenal biopsies and 16 esophageal biopsies. 56% male, 44% female.Common age group more than 58 years (38%).56% smokers, 44% nonsmokers and 57% alcoholic. Out of 16 esophageal biopsy, 9 diagnosed as squamous cell carcinoma, 4 esophagitis, 3 GERD. Out of 64 gastric biopsies, 33 diagnosed as chronic gastritis (33), hyperplastic polyp (7), ulcer (1), adenocarcinoma (23).69.70% cases of chronic gastritis were positive for H. pylori. Percentage of diffuse type of adenocarcinoma stomach was 69.5%. Out of 20 duodenal biopsies, 5 diagnosed as Adenomatous polyp followed by duodenal adenocarcinoma (4) and ampullary adenocarcinoma (1). Non-neoplastic lesion of duodenum included hyperplastic polyp (5) followed by duodenitis (4) and brunner gland hyperplasia (1). Conclusion: We tried to highlight the importance of routine endoscopic biopsies in patients with upper gastrointestinal symptoms and stain for H. pylori should be routinely done for all cases of chronic nonspecific gastritis. Clinicians should be aware of increasing incidence of GERD and and diffuse type of adenocarcinoma stomach in eastern zone.