Gastrointestinal stromal tumors (GIST), uncommon mesenchymal tumors, are driven by KIT or plateletderived growth factor receptor alpha (PDGFRA) mutations. They are most commonly diagnosed in older adults (median 62-63 years) presenting with GI bleeding or peptic ulcer-like symptoms, and most are found in the stomach (approximately 60%). GISTs are much more rarely diagnosed in the colon ( < 1%), with the sigmoid colon most commonly affected. We review the case of a 90-year-old white man who presented with one day of painless bright red blood per rectum. He denied abdominal pain, nausea, and vomiting. Past medical history included atrial fibrillation on warfarin, stroke, prostate cancer with retropubic radical prostatectomy, and hypertension. The patient was hemodynamically stable with a benign abdominal examination. Rectal examination revealed maroon blood but no hemorrhoids, fissures, or masses. Laboratory evaluation revealed hemoglobin 7.3 g/dL, WBC 7.6x10(9), INR 2.73, and creatinine 0.6 mg/dL. Electrolytes were unremarkable. A CT abdomen/pelvis revealed extensive bowel wall thickening focally, at the junction of the sigmoid and descending colon, with adjacent stranding (Figure 1). The patient underwent his index colonoscopy revealing a nearly-obstructing, necrotic, ulcerated mass with overlying clot 45 cm from the anal verge. (Figure 2). Several cold forceps biopsies were taken diagnosing a gastrointestinal stromal tumor, spindle cell subtype. Within the biopsy specimen there was no mucosal ulceration or mitoses and the ki-67 proliferative index was < 1%. By immunohistochemistry, the tumor cells expressed CD117 (c-kit), CD34, and SMA, and were negative for S100. Neither the c-KIT nor PDGFRA gene mutation was detected. Given the extent of disease and the patient's comorbidities, surgical resection was not pursued and he was initiated on imatinib 400 mg daily. At six months the patient was tolerating therapy well aside from lower extremity edema, a common side effect of imatinib.Figure 1Figure 2An estimated 12-15% of adult GIST lack KIT and PDGFRA mutations, which are mutually exclusive, and are classified as wild type. This case highlights the importance of using several histopathology markers to aid in the diagnosis of GIST. Over 95% of GIST express CD117 and 70-90% also express CD34, as was seen in this case. Those with the mutations are more likely to respond to imatinib therapy, a tyrosine kinase inhibitor., which allows therapy to be individualized.