Scintimammography with 99mTc-sestamibi can be used as a complementary technique to improve the mammogram's sensitivity and specificity for detection of breast carcinoma. We have observed in some patients focal areas of increased 99mTc-sestamibi uptake with no corresponding abnormalities on physical examination or mammogram. A phantom device and a special needle were designed to stereotactically localize these lesions before biopsy. METHODS After intravenous injection of 30 mCI (1110 MBq) of 99m Tc-sestamibi, a prone lateral image of the abnormal breast was obtained. With the patient in the prone position, the breast was compressed with two fenestrated plates in the prone position. The x and y coordinates of the abnormal hot spot of the breast were determined. The z coordinate of focal 99mTc-sestamibi uptake was determined by advancing a localizer needle through a selected predetermined hole of the fenestrated plate using real-time visualization on the persistence monitor. The tip of the opturator inside the needle is welded with 57Co to determine the depth of the hot spot in the breast. RESULTS Three women, all of whom had normal mammogram and breast physical examinations, were studied using 99mTc-sestamibi prone breast imaging. Pre-excisional biopsy needle localization of abnormal focal uptake was performed. Two women demonstrated infiltrative ductal carcinoma, and the third had proliferative fibrocystic disease of the breast. CONCLUSIONS Our initial experience demonstrates that nuclear medicine guided stereotactic needle biopsy of the breast in patients with positive scintimammograms is technically feasible. In the future, this technology will enable us to detect breast carcinoma in the absence of clear-cut clinical and mammographic findings.