3D-printed guides, which have recently been introduced in orthopedic oncology, improve resection accuracy compared with traditional bone resection methods, but there are inaccuracies associated with them. These inaccuracies could lead to disastrous outcomes such as positive tumor resection margins. In this Sawbone study, we sought to quantitatively investigate the margin of error for various jig types and to determine a "safety margin" that could serve as a guide for surgeons and jig engineers in creating 3D-printed jigs that would reduce the risk of potential disastrous results such as positive margins. Various 3D-printed jigs were used to simulate wide resection of a distal femoral bone sarcoma on Sawbone specimens by 10 individuals with no specific prior expertise in cutting guides. We developed a mathematical model using kinematic theory. We defined a safety margin as the amount of change in the osteotomy lines that must be incorporated into the jig design to ensure that the surgeon is at least 98% likely not to have a positive tumor margin. Experiments were conducted to determine the mean deviation experienced in placing cutting guides on the bones. The mean deviation for the four types of cutting guides ranged from 2.86 mm to 6.54 mm. We determined that a jig design should have a safety margin of 4.8 mm for standard guides and 8.65 mm for gusset guides to minimize the possibility of cutting into the tumor as a result of human error in guide placement. Further studies involving cadavers and patients are warranted. [Orthopedics. 2022;45(3):169-173.].