Infantile myofibromatosis is a rare benign congenital tumour that often regresses spontaneously but may pose therapeutic challenges in its widespread visceral form. We present the case of a full-term neonate with generalized infantile myofibromatosis including ubiquitous subcutaneous and muscular nodules, a tumour in the mastoid and disseminated intestinal involvement. The intestinal tumours led to a mechanical ileus with intestinal perforation within the first days of life. After partial small bowel resection and necessary proximal jejunostomy the boy was dependent on total parenteral nutrition. Chemotherapy with vinblastine and methotrexate was started and was temporarily supplemented with imatinib. Feeding stayed impossible despite tumour shrinkage. At the age of 4.5 months, restoration of intestinal continuity with further stricturoplasties was performed which – for the first time – allowed complete oral feeding. Chemotherapy was continued for further two months. Currently, the child is in good general condition with growth and further disease regression. This report suggests that massive visceral involvement of infantile myofibromatosis may require extensive intestinal surgery, as conservative therapy cannot resolve the disease and its sequelae.