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The sensitivity and specificity of breast cancer screening with mammography in dense breasts are very low, and increasing attention has been paid to breast density and screening in highrisk groups. Therefore, a supplemental screening modality is needed. Mammography and supplementary ultrasound screening are mainly based on the differences between cancerous and normal breast parenchyma on an anatomical basis, whereas breast-specific gamma imaging is a functional imaging approach examining the physiological phenomena of blood flow and mitochondrial activity, which are increased in cancer cells. The purpose of this review is to discuss the diagnostic methods, clinical results, clinical application, and considerations of breast cancer screening with breast-specific gamma imaging using 99mTc-sestamibi.