Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract and have only recently been described based on their specific immunohistochemistry and the presence of particular kit-related mutations which potentially make them targets for tyrosine kinase inhibition. Most GISTs are respectable, with survival mainly depending upon mitotic count and completeness of resection. Our own and other studies suggest that, in locally advanced cases, complete surgical resection (R0 resection) and adjuvant molecular therapy with imatinib yield good outcomes in terms of survival and disease-free status at 12 and 18 months. This approach, in the light of such integrated surgical-molecular therapy and of the new pharmaceuticals currently under research, means that we can now offer a real chance of recovery and a longer survival period to patients even with advanced-stage illness or local recurrence.