The use of Tc-99m-Sestamibi in molecular breast imaging is common due to its preferential uptake in malignant tissue. However, quantification of the baseline uptake in normal, healthy breast tissue is not possible using planar-imaging devices. Using our dedicated breast SPECT-CT system, an IRB approved pilot study is underway to quantify mean activity in normal breast tissue, and to differentiate uptake between adipose and glandular tissues. A cohort of patients at normal breast cancer risk undergoing another diagnostic Sestamibi study was imaged using the breast SPECT-CT system. SPECT images were corrected and quantitatively reconstructed using previously developed methods, and registered with the CT images. The CT images were segmented, and the average activity concentration was measured for glandular, adipose, and total breast tissue. Results indicate no preferential uptake between tissues and low average uptake, which may be used to determine a universal threshold for cancer detection. © 2012 Springer-Verlag Berlin Heidelberg.