99mTc-Tetrofosmin (TF) is a lipophilic diphosphine compound routinely used for myocardial scintigraphy. Extracardiac utilization has occurred in evaluation of patients with malignant neoplasms and in parathyroid adenomas. Although its uptake mechanisms are not completely understood, they appear similar to those of 99mTc Setamibi (MIBI). The importance of flow and the metabolic status of cells with an intracellular uptake depending on mitochondria and the Na+/K+ pump have been hypothesized. It has also been demonstrated that Tetrofosmin shares with MIBI the property of being a substrate for P-glycoprotein (P-gp), a multidrug resistance transporter. In this review the possible clinical role in breast cancer is analysed. First experiences suggest that scintimammography with TF is useful in patients with indeterminate Mammography and to obtain complementary data to avoid surgery and/or biopsy. TF is a reliable tracer for diagnosis of primary cancer, of local recurrence of axillary lymph node metastases. Preliminary data stimulate a possible role in functional imaging of chemoresistance and in differential diagnosis of distant metastases with main reference to the evaluation of single hot lesions at bone scan.