The purpose of this study was to analyse whether the use of Tc sestamibi scintimammography improves the positive predictive value of X-ray mammography. A series of 73 women (median age 51 years, range 35-79 years) with non-palpable, mammographically suspicious, breast lesions was reviewed. There were 41 (56.2%) pre-menopausal, and 32 (43.8%) post-menopausal women. All patients underwent sestamibi scintimammography prior to open breast biopsy. Definitive histology showed breast cancer (pT1a=1 (1.9%), pT1b=47 (90.4%), pT1c=4 (7.7%)) in 52 (71.2%) patients, and benign breast lesions in 21 (28.8%). Patients with cancer were significantly older (P<0.01), while the greatest dimension (size) of the excised lesion did not differ (8.47+/-1.51 vs 8.30+/-1.53 mm; P =0.66) between the two groups. Overall, the positive predictive values of mammography and sestamibi scintimammography were 71.2% and 95.7%, respectively (P =0.004). Patients with false positive mammography were significantly younger than those in whom cancer was diagnosed correctly (45.35+/-7.56 vs 53.96+/-10.60 years; P =0.001), while age did not affect the sensitivity of sestamibi scintimammography, which reached 100% in patients with breast lesions > or =8 mm in size. In this subgroup the positive predictive value of mammography, sestamibi scintimammography, and mammography+sestamibi scintimammography together were 63.4%, 95.1% (P =0.001), and 97.6%, respectively, and the majority of the patients with benign lesions (13 of 15 (86.7%)) could have avoided biopsy. It is concluded that the use of Tc sestamibi scintimammography in conjunction with mammography may potentially reduce unnecessary surgical procedures, and should be performed in all patients with mammographically suspicious breast lesions of 8 mm or greater in size.