INTRODUCTION: Pylephlebitis occurs in the setting of abdominal inflammatory processes and commonly begins with thrombophlebitis of mesenteric veins draining areas of infection. If unrecognized, it can carry a 30-day mortality as high as 32%. 1 Common etiologies include pancreatitis and diverticulitis, whereas no cases associated with metastatic colon cancer had been reported. 2,3 Thus, a high index of suspicion is necessary to make a timely diagnosis of a rare condition. CASE DESCRIPTION/METHODS: A 64-year-old man presented with 3-week history of constipation and fever of 103° F. Physical exam revealed scleral icterus, and tenderness to palpation of the abdomen. Lab studies were significant for leukocytosis of 21,000 cells/mL. Blood cultures remained negative. Abdominal CT revealed widespread tumor in the liver and thrombosis of the superior mesenteric vein (SMV) extending into the portal vein, causing edema in the colonic mesentery (Figure 1). Presence of gas within the clot in the SMV was noted. Core biopsy of a liver mass revealed adenocarcinoma. Colonoscopy revealed a cecal mass, confirmed to be colonic adenocarcinoma (Figures 2 and 3). The patient was started on antibiotics for suspected pylephlebitis, later transitioned to oral Ciprofloxacin and Metronidazole, for 4 weeks. Intravenous heparin was changed to Enoxaparin. DISCUSSION: Without the development pylephlebitis, our patient's colon cancer likely would have spread beyond the liver. While bacteremia was not detected, it is not reported with 100% frequency. 1 The presence of gas within the clot along with fever and leukocytosis raised suspicion for infection of the venous clot. Therapy includes antibiotics for up to 6 weeks with consideration for anticoagulation. While the routine use of anticoagulation for pylephlebitis remains controversial, given the risk of thrombus extension causing mesenteric ischemia, the benefits outweighed the risks. Pylephlebitis due to metastatic colon cancer is a rare etiology, and should be considered in patients presenting without commonly reported risk factors.