The scattering of longitudinal and shear waves from spherical, nucleated cells and three-dimensional tissues with simple and hierarchical microstructures was numerically modeled at the microscopic level using an iterative multipole approach. The cells were modeled with a concentric core-shell (nucleus-cytoplasm) structure embedded in an extracellular matrix. Using vector multipole expansions and boundary conditions, scattering solutions were derived for single cells with either solid or fluid properties for each of the cell components. Tissues were modeled as structured packings of cells. Multiple scattering between cells was simulated using addition theorems to translate the multipole fields from cell to cell in an iterative process. Backscattering simulations of single cells indicated that changes in the shear properties and nuclear diameter had the greatest effect on the frequency spectra. Simulated wave field images and high-frequency spectra (15-75 MHz) from tissues containing 1211-2137 cells exhibited up to 20% enhancement of the field amplitudes at the plasma membrane, significant changes in spectral features due to neoplastic and other microstructural alterations, and a detection threshold of approximately 8.5% infiltration of tumor cells into normal tissue. These findings suggest that histology-based simulations may provide insight into fundamental ultrasound-tissue interactions and help in the development of new medical technologies.