Pylephlebitis is also called suppurative thrombophlebitis of the portal venous mesenteric system. It is often seen as a complication of intra-abdominal infection, mainly diverticulitis and appendicitis. It is a rare disease with high mortality. Because of its nonspecific presentation, diagnosis is usually missed. So, it is important to consider pylephlebitis as one of the differential diagnoses if the patient presents with signs of abdominal sepsis. Pylephlebitis usually begins with thrombophlebitis of small veins draining an area of intra-abdominal infection and extends into larger veins that cause septic thrombophlebitis of the portal vein and further extending to mesenteric veins. Here, we present the case series of 6 patients older than 60 years who have underlying abdominal cancer at the Moffitt Cancer Center and Research Institute and review the literature.