To assess the utility of humeral shaft fractures as predictors of organ injuries and skeletal injuries in multiply injured patients involved in motor vehicle collisions (MVCs). A prospectively collected database of multiply injured motor vehicle occupants with an Injury Severity Score (ISS) greater than 12 admitted to a level I regional trauma centre during a 102-month period (January 1992 to June 2000) was reviewed to assess skeletal and organ injuries associated with a humeral shaft fracture. The effect of occupant location within the vehicle, the point of collision, and the use of a seat belt restraint was also examined to identify trends in injury patterns. Data from 1070 motor vehicle occupants - 65 with concomitant humeral shaft fractures and 1005 without humeral shaft fractures - revealed that 63% of motor vehicle occupants who sustained humeral fractures were drivers, compared with 77% in the non-humeral fracture group. Those patients who sustained a humeral shaft fracture had a significantly greater number of liver injuries (p = 0.022), forearm/hand fractures (p < 0.001), tibial fractures (p < 0.01) and femoral fractures (p < 0.01) compared with controls. A lateral collision impact showed a trend towards increased splenic and hepatic injuries within the humeral shaft fracture group. The presence of a humeral shaft fracture in a multiply injured patient involved in a MVC is significantly associated with an increased incidence of both upper and lower extremity fractures and liver injury. Moreover, humeral shaft fractures may serve as a predictor of potential intra-abdominal pathology in multiply injured trauma patients involved in MVCs.