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Introduction: A variety of disorders affect the upper gastrointestinal tract. Study of endoscopic biopsies is imperative to make an accurate diagnosis, which will aid in early diagnosis and appropriate management of the patient. Aim: To determine the histomorphological spectrum and the occurrence of upper gastrointestinal lesions; and also to associate endoscopic diagnosis with histopathology. Materials and Methods: This was a retrospective, descriptive study conducted from May 2017 to April 2019 on 106 cases, done at BGS Global Institute of Medical Sciences, Bengaluru, Karnataka, India. Microscopic findings were studied by two pathologists. Results: A total of 106 cases were studied. Majority of the patients (56%) presented with abdominal pain followed by dyspepsia and dysphagia. Stomach was the most common site of biopsy followed by oesophagus and duodenum. Majority of oesophageal and gastric biopsies were found to be neoplastic i.e., 70.8% and 56.3% respectively; however, non-neoplastic lesions formed the majority in duodenal biopsies (88.9%). The most common malignancy was squamous cell carcinoma, which occurred predominantly in the middle third of the oesophagus. The most common malignancy in the stomach was adenocarcinoma. Correlation between endoscopic diagnosis and histopathology was done in 70 cases; and there was consensus in 78.5% of the cases (55/70 cases). Conclusion: Endoscopy with assisted biopsy is the gold standard for diagnosis of upper gastrointestinal disorders. An interdisciplinary approach towards diagnosis and treatment involving the pathologist and clinician is important.