The complementary role of sestamibi scintimammography (SSM) in patients with breast cancer (BC) is well established. The aim of this study was to establish whether a relationship exists between sestamibi uptake, evaluated as a tumour-to-background ratio (TBR), and the main prognostic factors of BC. SSM with the measurement of TBR was performed preoperatively in 102 women (median age 57 years, range 32-81 years) who underwent curative surgery for primary BC. Final pathology showed 4 (3.9%) with pT1a, 17 (16.7%) with pT1b, 44 (43.1%) with pT1c and 37 (36.3%) with pT2 breast carcinomas. The overall sensitivity of SSM was 80.4%. An ANOVA showed significant (P<0.01) differences between the TBR of patients with G1 vs. G3 tumours, and between the TBR of those with G2 vs. G3 breast carcinomas. Moreover, there was a difference (P=0.021) between the TBR of patients (n=12, 11.8%) with CEA serum levels >10 ng/ml (2.031+/-0.420), and those with normal (n=90, 88.2%) CEA values (1.713+/-0.446), whilst no difference (P=NS) was found between patients (n=27, 26.5%) with CA 15-3 >30 U/ml (1.893+/-0.401) and those with normal (n=75, 73.5%) CA 15-3 values (1.699+/-0.462). There was a mild inverse correlation between TBR and both the oestrogen (R=0.25, P=0.011) and the progesterone receptor (R=0.23, P=0.02) rate. The logistic regression analysis showed that only size and CA 15-3 serum levels represent true independent parameters, but the function was able to predict only 11 out of 21 (52.4%) patients with false-negative SSM. TBR is independent of age and mainly correlates with the size of the tumour. There are no reliable preoperative prognostic factors that are really useful for improving SSM sensitivity in patients with small breast carcinomas.