Infantile myofibromatosis involving the skull is a benign disease if there is a solitary lesion. However, the multifocal form with skull involvement may portend a lethal course in the 1st year of life if there is involvement of the heart, lungs, or gastrointestinal tract. The authors report the case of a 3-year-old boy with an enlarging left parietal skull lesion that had been present since infancy. Increasing pain and the need to obtain tissue for diagnosis led to resection of the lesion by means of a small craniectomy. Further evaluation revealed no other lesions. A distinctly rare disease is presented, and the need for staging in children younger than 2 years of age is suggested to rule out cardiac, pulmonary, or gastrointestinal involvement.