This paper reviews the evaluation of malignancy and prognostic parameters used in gastrointestinal stromal tumours (GIST). Incorporated is a case report of a duodenal GIST treated at our institution. GIST represents a spectrum of mesenchymal tumours from benign to malignant variants, which can arise from anywhere in the gastrointestinal tract. A central pathogenetic event recognised in most GISTs is KIT activation (a tyrosine kinase receptor) believed to be the result of oncogenic mutations. Imatinib mesylate, (a humanised monoclonal antibody), highly effective in vitro in reducing KIT tyrosine activity, has revolutionised the treatment of metastatic GIST, and is discussed along with other treatment options. Traditionally the three key prognostic factors used in GIST have been mitotic rate, tumour size, and anatomic location. However, the unpredictable behaviour of GIST has led to the development of immunohistochemical differentiation markers including CD117 (detecting KIT protein). In addition genetic markers have been used as prognostic parameters, including KIT activating mutations, cytogentic aberrations and telomerase activity.