The WHO classification of digestive system tumours presented in the first volume of the WHO classification of tumours series, 5th edition, reflects important advancements in our understanding of tumours of the digestive system (Table 1). For the first time, certain tumour types are defined as much by their molecular phenotype as their histological characteristics; however, in most instances histopathological classification remains the gold standard for diagnosis. The WHO classification of tumours series is designed to be used worldwide, including those settings where a lack of tissue samples or of specific technical facilities limits the pathologist's ability to rely on molecular testing. Since the publication of the 4th-edition digestive system tumours volume in 2010,1 there have been important developments in our understanding of the aetiology and pathogenesis of many tumours. However, the extent to which this new information has altered clinical practice has been quite variable. For some of the tumours described in this volume there is little molecular pathology in clinical use, despite the fact that we now have a more detailed understanding of their molecular pathogenesis. A tumour's molecular pathology, as defined for the purposes of this publication, concerns the molecular markers that are relevant to the tumour's diagnosis, biological behaviour, outcome and treatment, rather than its molecular pathogenesis. However, the role of molecular pathology is expanding; for some tumour entities, molecular analysis is now essential for establishing an accurate diagnosis. Some of these analyses require investigation of somatic (acquired) genetic alterations, gene or protein expression, or even circulating tumour markers. For certain tumour types, specific analytical tests are needed to predict prognosis or tumour progression, and these tests are carefully outlined in this volume. In the following paragraphs, we have summarised some of the more notable changes since the 4th edition. In instances where the new WHO clas...