Although solitary presentations of infantile myofibromatosis tend toward spontaneous regression, multicentric forms fare worse. Previous case reports have depicted observation, surgical resection, and systemic therapies as treatment options. This paper reports well-tolerated, successful outcomes in a series of patients with high-risk infantile myofibromatosis in need of life-sustaining interventions treated with a combination of vincristine and dactinomycin. The clinical presentation, pathology, and radiographic findings are described.