Desmoid-type fibromatosis (DTF) is a rare locally aggressive soft tissue neoplasm which occurs in children and adults, with a peak incidence in young adults. For the majority of the patients DTF is a chronic and symptomatic disease which affects health-related quality of life. Systemic treatment regimens tend to differ for patients treated by pediatric oncologists compared to medical oncologists. This systematic review identified 14 clinical trials in children and adults with DTF. Tumor response and progression-free survival rates varied widely between studies and study populations. Treatment choices for patients with DTF are based on a paucity of (randomized) trials. Treatment principles of DTF are similar in pediatric and adult oncology, but the treatment itself is different. This seems mostly driven by a lack of TKI accessibility in pediatric oncology. An insufficient number of studies examined patient-reported outcomes, which are extremely important for patients with a chronic disease like DTF. This article is protected by copyright. All rights reserved.