A hand-raised, 5-mo-old, intact male Brazilian porcupine (Coendou prehensilis) was evaluated for chronic diarrhea, failure to thrive, and anorexia. On presentation the porcupette was dull, dehydrated, and passing yellow, malodourous, watery diarrhea. Cytologic examination of feces revealed a large number of organisms, morphologically consistent with Blastocystis. Blastocystis polymerase chain reaction (PCR) performed on feces was positive. Direct sequencing on two sequential samples confirmed the presence of Blastocystis ratti and a novel Blastocystis sequence. The porcupette was treated supportively, which included a 4-wk metronidazole course. Diarrhea resolved within 2 wk of treatment, and the animal's growth rate dramatically improved. Recheck PCR was negative for Blastocystis. Although an important and controversial cause of diarrhea in immunocompromised humans, this organism is not well recognized as a potential pathogen and zoonosis in zoo animals. Clinicians should be aware of the potential for disease associated with this organism, especially in immunocompromised animals.