Although recent nanoindentation studies have revealed the existence of substantial variations in tissue modulus within single specimens of trabecular bone, little is known regarding the biomechanical effects of such intraspecimen variations. In this study, high-resolution finite element modeling was used to investigate these effects. With limited literature information on the spatial distribution of intraspecimen variations in tissue modulus, two plausible spatial distributions were evaluated. In addition, three specimens (human femoral neck, human vertebral body, and bovine proximal tibia) were studied to assess the role of trabecular architecture. Results indicated that for all specimen/distribution combinations, the apparent modulus of the whole specimen decreased nonlinearly with increasing coefficient of variation (COV) of tissue modulus within the specimen. Apparent modulus decreased by <4% when tissue modulus COV was increased from 0% to 20% but decreased by 7–24%, depending on the assumed spatial distribution, for an increase in tissue modulus COV from 20% to 50%. For compressive loading to the elastic limit, increasing tissue modulus COV from 20% to 50% caused up to a 28-fold increase in the amount of failed tissue, depending on assumed spatial distribution and trabecular architecture. We conclude that intraspecimen variations in tissue modulus, if large, may have appreciable effects on trabecular apparent modulus and tissue-level failure. Since the observed effects depended on the assumed spatial distribution of the tissue modulus variations, a description of such distributions, particularly as a function of age, disease, and drug treatment, may provide new insight into trabecular bone structure-function relationships.