We describe a case of an ASNIS III 5.0 mm partially threaded cannulated screw unthreading itself as it was being inserted during fracture fixation of a humerus. The majority of complications associated with cannulated screws involve breaking of the screw, as opposed to unthreading. We believe that the self tapping design of the screw, in combination with the cannulated design, creates a potential area of weakness when used on hard bone.