Optically derived tissue properties across a range of breast densities and the effects of breast compression on estimates of hemoglobin, oxygen metabolism, and water and lipid concentrations were obtained from a coregistered imaging system that integrates near-infrared spectral tomography (NIRST) with digital breast tomosynthesis (DBT). Image data were analyzed from 27 women who underwent four IRB approved NIRST/DBT exams that included fully and mildly compressed breast acquisitions in two projections—craniocaudal (CC) and mediolateral-oblique (MLO)—and generated four data sets per patient (full and moderate compression in CC and MLO views). Breast density was correlated with HbT (, ), water (, ), and lipid concentrations (, ), but not oxygen saturation. CC and MLO views were correlated for individual subjects and demonstrated no statistically significant differences in grouped analysis. Comparison of compressed and uncompressed imaging demonstrated a significant decrease in oxygen saturation under compression (58% versus 50%, ). Mammographic breast density categorization was correlated with measured optically derived properties.