The molecular targets of sunitinib are receptor tyrosine kinases (RTKs), and this drug has also been known to exert blocking effects on the activation of KIT, which is similar to the mechanism of action of imatinib. Moreover, sunitinib has an additional anti-angiogenic effect through its inhibition of the vascular endothelial growth factor receptor activation. We report here a 70-year-old patient diagnosed with a recurrent gastrointestinal stromal tumor (GIST), which invaded the transverse colon and led to a perforation during sunitinib treatment. A computed tomography scan and 3-dimensional reconstruction showed necrosis of the recurrent hepatic mass and perforation of the invaded transverse colon. After percutaneous drainage of the intraperitoneal abscess, antibiotic treatment and restricted diet, the condition of the patient improved. The present case is the first to report that sunitinib, which is administered to treat GIST resistant to imatinib, can cause unexpected colon perforation and subsequent peritonitis.