Little data regarding the use of chemoprophylaxis for venous thromboembolism in patients with bone tumors exist, requiring extrapolation from other aspects of orthopaedics such as total joint arthroplasty. Although these are similar populations, there are significant differences (e.g., bleeding risk) that make pathway protocols for limb salvage surgery undesirable. Current American College of Chest Physicians guidelines state that patients with high venous thromboembolic risk plus high bleeding risk can be considered for mechanical prophylaxis risk alone, while recent recommendat/ions from the American Academy of Orthopaedic Surgeons for patients at a high risk for venous thromboembolism and bleeding include aspirin, coumadin, or no anticoagulation. Both authoritative bodies leave significant room for individual clinician interpretation while caring for patients undergoing total joint arthroplasty, limb salvage surgery or other major orthopaedic procedures. While the role of anticoagulation in total joint arthroplasty has become more defined, its role in limb salvage surgery remains unclear. Major orthopaedic surgery and cancer are known risk factors for thromboembolic disease; however, the same subset of patients usually undergo extensive procedures that have an inherently high risk of complications such as bleeding and wound infections, which may be exacerbated by anticoagulants. Physicians performing limb salvage surgery should use a selective approach to determine which anticoagulation, if any, should be used in this population.