Great advances in many areas of tumor biology have led to a better understanding of the pathogenesis, pathology, and molecular biology of epithelial and stromal malignancies of the upper gastrointestinal tract. Many of these advances have led to specific improvements in diagnosis, prognosis, treatment, and thus, survival in patients affected by these tumours. This edition of the Fascicle was written to highlight these advances, and more specifically, to help pathologists diagnose diseases more accurately and understand how pathology contributes to clinical treatment in the new age of personalised and targeted therapy.