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Background and Aims: Oesophageal malignancies tend to have poor prognosis and thus there is a need to identify newer therapeutic targets for their treatment. This study aimed at studying the incidence and histopathological spectrum of oesophageal malignancies with special emphasis on immunohistochemical expression of HER2/Neu in adenocarcinomas.Material and Methods: This study was a retrospective descriptive study conducted in a tertiary care centre in South India. Endoscopic biopsies and resection specimens of oesophageal malignancies were included in the study. Immunohistochemical analysis for HER2/Neu was performed on all oesophageal adenocarcinomas.Results: Squamous cell carcinoma constituted the most common malignancy in this study. Approximately 20% of oesophageal adenocarcinomas showed positivity for HER2/Neu. A prominent association of Barrett’s metaplasia with oesophageal adenocarcinoma was noted.