Mesenchymal Gastrointestinal (GI) tumours are heterogenous group of tumours. Prior to 2005, immunohistochemistry (IHC) was not used in diagnostic pathology to characterize these tumours at our centre.To subclassify mesenchymal tumours in the GI tract and related locations into Gastrointestinal stromal tumour (GIST) and non-GIST tumours using specific IHC antibody markers.Formalin Fixed Paraffin Embedded tumour tissue over the period 1991- 2004 were retrieved, from the files and records of the Department of Pathology, University College Hospital, Ibadan, Nigeria. Haematoxylin and Eosin slides of such cases were reviewed. The IHC expressions of c-Kit, CD 34, α-smooth muscle actin, desmin and S-100 were evaluated in these tumours.Based on morphology and IHC staining pattern, 24 of the 46 cases were identified as GIST by c-kit positivity. Nine of the cases were smooth muscle tumours (4- leiomyoma and 5- leiomyosarcoma), 8 cases of undifferentiated sarcomas, 4 cases of desmoid and one case of inflammatory myofibroblastic tumour. For GISTs: The male:female ratio is 1.2. The age range of the patients was 11-75 years with a mean age of 55.1 years.Tumour size ranged from 7-32 cm with an average of 19.8cm and average mitotic count of 20 per 50 high power field. The location of the GIST tumours were as follow- stomach- 9 cases (37.5% of the 24 GIST cases), colon and rectum -6 (25%), Abdominal cavity (omentum/ mesentery)- 6 (25%), retroperitoneum-2(8.3%), small intestine-1 (4.2%).The use of IHC in this study has helped to segregate and distinguish GI mesenchymal tumours into different sub-types, majority being Gastrointestinal stromal tumours.