The clinic-histopathological profiles of upper GI lesions through endoscopic biopsies, focusing on their correlation with patient demographics. Conducted at the Dr.Shankarrao Chavan Government Medical College & Hospital, this cross-sectional analysis encompasses biopsies from adults presenting with symptoms indicative of upper GI tract pathologies, excluding previously diagnosed GI conditions and inadequate samples. The methodology entailed collecting and processing 4-6 biopsy samples per patient, followed by Hematoxylin and Eosin staining, with Giemsa stain utilized for suspected gastritis or dysplasia cases to detect H. pylori. The neoplastic lesions were classified per WHO guidelines, and data were analysed using Microsoft Excel. Results from 103 biopsies indicated a predominance of esophageal lesions (70.9%), with squamous cell carcinoma being the most frequent neoplastic finding (73.9%). Chronic gastritis was the common non-neoplastic condition, with a significant correlation observed between H. pylori presence and gastritis cases. Notably, the majority of neoplastic lesions were found in males, with dysphagia being the most associated symptom. In conclusion, the study highlights the indispensable role of endoscopic biopsies in diagnosing upper GI tract lesions, underscoring the need for integrating advanced diagnostic techniques to enhance patient care. The findings echo the broader literature's emphasis on the diagnostic synergy between endoscopic and histopathological evaluations, despite variations due to geographical and demographic factors.