Gastrointestinal stromal tumors are rare neoplasms arising from mesenchymal cells of the gastrointestinal tract, that strongly express a class III receptor tyrosine kinase, called KIT, due to some mutations in the KIT proto-oncogene. Two thirds of GISTs are found in the stomach, 20% to 50% in the small bowel (one third in the duodenum), and 5% to 15% in colon and rectum; GISTs, however, may rarely be found also in the oesophagus, omentum, mesentery or the retroperitoneum. Their treatment is strictly surgical, and only R0 resection can achieve goodTreatment with Imatinib seems to be promising in case of unresectable or metastatic GIST, even if some trials are studying its effects after curative resection. GIST of the mesocolon are rare, and as in the other locations, require extensive surgery. The Autohrs report a case of giant malignant GIST arising from transverse mesocolon, treated by en-bloc resection of the tumor with a segment of transverse colon and great omentum.