The aim of this study was to compare the results obtained using X-ray mammography (MG) and 99mTc-sestamibi scintimammography (SSM) in patients with breast lesions < or = 2 cm. One hundred and thirty-four women (median age 52 years, range 32-78), who had already been selected for open breast biopsy, underwent both MG and SSM prior to surgery. Final pathology showed 27 (20.1%) benign breast lesions and 107 (79.9%) breast cancers (pT1a=5 [4.7%], pT1b=50 [46.7%], pT1c=52 [48.6%]). The sensitivity, positive predictive value, negative predictive value and accuracy were 81.3%, 97.6%, 55.6% and 83.6% for SSM and 83.2%, 89.9%, 48.6% and 79.1% for MG, respectively. The results were similar (p=NS), but patients with breast cancer (BC) undetected by MG were significantly (p<0.05) younger than those in which the tumor was correctly diagnosed, while the age did not affect SSM sensitivity. SSM was more (p<0.05) specific than MG in BC detection both in the overall group of patients (92.6% vs 63.0%) and in those with < or = 10 mm breast lesions (94.7% vs 63.2%). In conclusion, in patients with suspected BC sized < or = 2 cm, SSM may help in surgical planning because of its high specificity, and should be considered complementary to MG, especially in younger women.