The aim of this work was to investigate 99mTc-sestamibi uptake and histopathological characteristics of breast tumors. Static 99mTc-sestamibi scintimammography (SMM) has been performed in 101 breast tumors (98 patients). SMM were scored from 0 to 4 according to intensity of 99mTc-sestamibi uptake and classified in two groups: SMM with absence or low tumor uptake (0, 1, 2) and SMM with high tumor uptake (3, 4). Tumor histopathological characteristics have been determined on core or excisional biopsy. The 99mTc-sestamibi uptake (low vs. high) correlated to classical prognostic factors: positively with Scarff-Bloom and Richardson (SBR) grade (p < 0.0005), axillary involvement (p < 0.0005), and tumor size (p < 0.0005) and negatively with estrogen receptors (p < 0.001). Fixation of 99mTc-sestamibi in invasive lobular carcinoma was lower than in invasive ductal carcinoma (p < 0.01) despite a similar mean tumor size (28 +/- 14 mm vs. 24 +/- 14 mm). Relations between 99mTc-sestamibi uptake and tumor size, histologic type, and axillary involvement were independent variables also significant in multivariate analysis (p < 0.0005, p < 0.005, p < 0.05, respectively). Moreover, the five-year survival rate was higher when 99mTc-sestamibi breast tumor uptake was low (p < 0.005). This difference is also significant using the Cox model (p < 0.05). Uptake of 99mTc-sestamibi (low vs. high) discriminates breast tumors with different histopathological characteristics and prognosis.