Introduction: Heterotopic mesenteric ossification (HMO) is a rare clinical entity with less than 40 reported cases in the literature. Frequently associated with prior abdominal surgery or trauma, the precise etiology and optimal approach to its management remain undefined. Case Report: The index patient is a 58-year-old male who originally presented with perforated diverticulitis. Following resection, the patient developed an enterocutaneous fistula. After a trial of conservative management, the patient underwent exploration and was found to have widespread intra-abdominal calcification. Sheets of calcific tissue were resected, and a diagnosis of HMO was confirmed via pathology. The patient had a postoperative course complicated by bleeding and redevelopment of enteric fistula. Following a prolonged hospital course requiring multiple operations, the fistula persists, and the patient remains on parenteral nutrition. Discussion: The etiology of HMO is unknown. Diagnosis requires a high degree of clinical suspicion, as radiologic findings are often misleading. A review of 18 cases demonstrates significant morbidity associated with operative intervention. Nonsteroidals, in particular indomethacin, have been shown to decrease heterotopic ossification, but their role in mesenteric disease is not clearly defined. Conclusion: HMO is a rare but complicated pathologic process. A trial of conservative management with NSAIDs, bowel rest, and total parenteral nutrition is prudent, given the high rate of morbidity and mortality associated with operative intervention.