Ninety-eight women and 3 men (age range, 16-88 years; mean 46 years) with 103 lesions underwent technetium-99m methoxyisobutylisonitrile (99mTc-sestamibi, 99mTc-MIBI) breast scintigraphy prior to biopsy to assess the value of this technique for the detection of breast carcinomas and for their differentiation from benign breast masses. Scans of 29 patients were 99mTc-sestamibi-positive and 72 were 99mTc-sestamibi-negative. Scintimammographic findings were true positive in 21 (72%) biopsy confirmed carcinomas and true negative in 65 (89%) benign lesions. 99mTc-sestamibi scans were false-negative in 7 cases of breast cancer: 4 infiltrating ductal carcinomas and 3 infiltrating ductal with an intraductal component. There were 8 false positive scans which included 4 fibroadenomas, 2 papillomas and 2 areas of chronic inflammation. The mean size of the 99mTc-sestamibi-positive carcinomas was 2.9 ± 1.2 cm, which contrasts to the size of 99mTc-sestamibi-negative breast malignancies, which averaged 1.8 ± 0.6 cm (P < 0.005). The sensitivity of using 99mTc-sestamibi for detection of breast carcinoma was 75% and its specificity 89%. The positive and negative predictive values were 88% and 93% respectively. Interobserver agreement between the 2 independent and blinded nuclear medicine physicians was 98%. Size of tumor is a critical factor in the detection of sestamibi uptake. 99mTc-sestamibi can help in the investigation of breast masses.