A three-dimensional finite element model of a lumbar vertebral body was developed to study the effects of geometry, material properties and loading conditions on stresses in the presence of metastatic lesions. Parameters studied included location and size of the lesion, modulus of the cortical and trabecular bone within and near the lesion, generalized osteoporosis and load distribution. The results, expressed as ratios of peak values of displacement and stress, relative to a normal baseline case, indicated that the location of a defect which did not penetrate the cortex had a minor influence on the peak displacement and stresses, as did the presence of lesions occupying less than 40% of the volume of the vertebral centrum. A lesion occupying 40% of the centrum volume increased the endplate displacement by 2.9 times, the peak tensile stress in the cortical shell by 2.2 times, and the peak von Mises stress in the endplate by 2.8 times. When this lesion penetrated the cortex, these values increased to 3.8, 3.3 and 4.4 times, repsectively. The most severe case involved a defect penetrating the anterior cortex, osteoporotic bone properties and anteriorly eccentric loading. In this case, the peak values increased to 8.4, 3.4 and 5.9 times their baseline values, respectively. The results are consistent with a model of the vertebral body as a stiff frame of cortical bone surrounding a relatively compliant core of trabecular bone. Only variations in geometry and properties large enough to lessen significantly the structural stiffness affect the peak stresses and displacements. Such a case occurs when an osteoporotic vertebral body containing a lesion of approximately half its volume is subjected to an anterior eccentric load distribution, as occurs in forward flexion. Under these conditions, large increases in the stress magnitudes put the vertebral body at extreme risk of fracture.