Imaging of oxygen saturation provides a spatial map of the tissue metabolic activity and has potential in diagnosis and treatment monitoring of breast cancer. Oxygen-saturation imaging is possible through near-infrared (NIR) tomography, but has low signal-to-noise ratio (SNR). This can be augmented by using NIR tomography as an add-on to MRI. Presented are results from a free-standing NIR system and a hybrid MR-guided system for breast imaging. In results from imaging 60 healthy volunteers in the initial NIR system, oxygen saturation was a significant discriminator between the BIRADS classifications of adipose tissue, heterogeneously dense, and extremely dense tissue. By using the MR-guided NIR system, more accurate tissue-specific data were obtained on adipose and fibroglandular volumes, with 11 healthy volunteers. In these data, oxygen saturation in the adipose tissue correlated with percentage of adipose tissue. In two case studies of infiltrating ductal carcinomas, oxygen saturation was reduced at the site of the tumor, as compared with the surrounding healthy tissue, agreeing with conventional thought that hypoxia exists in larger solid tumors. The MRI-guided NIR images of oxygen saturation provide higher resolution and superior SNR and will likely be used in the future to study and characterize specific tissue volumes.