The evaluation of breast tissue using nuclear imaging is dependent upon the delivery and uptake of the isotope by breast tissue. This is dependent upon blood flow to the breast and functioning mitochondria. This 2-part study investigated (1) differences in uptake of sestamibi when blood flow is enhanced (breast enhanced scintigraphy test [BEST]), and (2) differences in isotope uptake in normal (Nl) breast tissue, inflammatory changes in breast tissue (ICB), and breast cancer (CA). In the first part of the study, 10 women were compared using both Miraluma and BEST imaging; in the second part, 195 people were studied using BEST imaging only. The results were compared with histopathologic specimens. Little difference was noted between Miraluma and BEST imaging in the first part. Women with ICB showed a statistically significant (P < .05) increase in isotope uptake using BEST imaging. This difference was even more significant (P < .005) in women with CA. During the second part of the study, BEST imaging demonstrated an exponential increase in tracer uptake. When maximal count activity was compared, there was a statistically significant (P <.001) difference between Nl and ICB, between ICB and atypia (A), and between A and CA. BEST imaging demonstrated significant increases in isotope delivery when compared with Miraluma imaging. These differences allowed differentiation of breast tissue, including the detection of early changes in breast tissue.