Pythium insidiosum is an aquatic fungus-like organism that causes a serious chronic granulomatous disease called pythiosis in animals and humans in tropical and subtropical regions of the world. In North America, pythiosis is most often diagnosed in the Gulf Coast states. Early recognition of the disease is crucial to successful treatment, which includes surgical resection of granulomatous lesions and administration of antifungal agents. Despite increasing availability of diagnostic tests, intestinal pythiosis is insidious and is often not detected until lesions are extensive. Intestinal pythiosis was diagnosed in a 12-week-old puppy from South Carolina examined because of vomiting, diarrhea, and anorexia. Pythiosis was not initially suspected because of the young age of the patient and because pythiosis is uncommon in this area.