The oesophagus and stomach present a wide spectrum of benign and neoplastic conditions. Understanding the pathology of these conditions has always been important to the surgical management of these diseases. The advent of modern molecular pathological techniques has greatly expanded our knowledge of the underlying pathogenesis of these conditions and now directly affects practice. The integration of this new knowledge with standard histopathological techniques presents new challenges to the pathologists and surgeon alike. This chapter discusses benign and malignant pathology of the oesophagus and stomach, with repeated emphasis on new knowledge where these influence practice. By far, the commonest conditions affecting the oesophagus and stomach are benign. However, these conditions can impact heavily on affected individuals. Although relatively rare, cancers carry a huge burden on the individual and society. Specific management and prognosis for these conditions are dependent on accurate diagnosis, which is the realm of pathology. In this regard, the patient presentation, clinical and diagnostic findings together with chemical pathology (Biochemistry), where appropriate, are essential in guiding the pathologist to apply sophisticated pathological essays that clinch the diagnosis. In some circumstances, pathology is also important in identifying the aetiology, pathophysiology and malignant potential of some conditions.