Delayed union or nonunion are relatively rare complications after fracture surgery, but when they do occur, they can result in substantial morbidity for the patient. In many cases, the etiology of impaired fracture healing is uncertain and attempts to determine the molecular basis for delayed union and nonunion formation have been limited. Prospectively isolating skeletal stem cells (SSCs) from fracture tissue samples at the time of surgical intervention represent a feasible methodology to determine a patient's biologic risk for compromised fracture healing. This report details a case in which functional in vitro readouts of SSCs derived from human fracture tissue at time of injury predicted a poor fracture healing outcome. This case suggests that it may be feasible to stratify a patient's fracture healing capacity and predict compromised fracture healing by prospectively isolating and analyzing SSCs during the index fracture surgery. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.