Pylephlebitis is a septic thrombophlebitis of the portal vein that is associated with multiple suppurative abdominal infections, such as diverticulitis, appendicitis, cholangitis, and cholecystitis. We describe a case of pylephlebitis in a patient with fever and diffuse, poorly localized abdominal pain who was eventually diagnosed with appendicitis. We aim to increase awareness of this condition among emergency physicians, as timely initiation of antibiotics and expedited surgical resection may improve outcomes in this potentially fatal disease.