A prospective study designed to measure the accuracy of mammography (MRx), ultrasound (US), fine-needle aspiration cytology (FNAC) and one of the most recently introduced techniques, vacuum biopsy (VB), in the diagnosis of breast cancer is reported. A sample of 146 breast lesions on 135 patients were examined. The design of the study made it possible to compare MRx, US, FNAC and VB directly, because it excluded several confounding variables. Statistical indicators--sensitivity, specificity, predictive values (PPV and NPV), false-negative and false-positive rates (FN and FP), suspicious plus indeterminate rate and likelihood ratios (LR)--were calculated. The NPV of MRx and US were remarkably high (92.4% and 97.9%, respectively), confirming previous reports. The complete sensitivity of FNAC was 80%, while specificity was 99.1% and LR of positive tests 88.8. The combined score of FNAC, US and MRx resulted in a good increase in complete sensitivity (97.1%), when compared with the results of the single diagnostic tests evaluated separately. The absolute sensitivity of VB was 97.1% and specificity was 100%. In conclusion, considered together, MRx, US and FNAC appear to be reliable diagnostic procedures and, when they are all negative, the possibility of a cancer is extremely low, although it cannot be completely ruled out. The VB test had the highest absolute sensitivity among all the methods compared. Therefore, this technique could be considered conclusive in diagnostically doubtful cases, avoiding open surgical biopsy.