To prospectively assess accuracy of mammography, clinical examination, ultrasonography (US), and magnetic resonance (MR) imaging in preoperative assessment of local extent of breast cancer. Institutional review board approval and informed patient consent were obtained. Results of bilateral mammography, US, and contrast-enhanced MR imaging were analyzed from 111 consecutive women with known or suspected invasive breast cancer. Results were correlated with histopathologic findings. Analysis included 177 malignant foci in 121 cancerous breasts, of which 89 (50%) foci were palpable. Median size of 139 invasive foci was 18 mm (range, 2-107 mm). Mammographic sensitivity decreased from 100% in fatty breasts to 45% in extremely dense breasts. Mammographic sensitivity was highest for invasive ductal carcinoma (IDC) in 89 of 110 (81%) cases versus 10 of 29 (34%) cases of invasive lobular carcinoma (ILC) (P < .001) and 21 of 38 (55%) cases of ductal carcinoma in situ (DCIS) (P < .01). US showed higher sensitivity than did mammography for IDC, depicting 104 of 110 (94%) cases, and for ILC, depicting 25 of 29 (86%) cases (P < .01 for each). US showed higher sensitivity for invasive cancer than DCIS (18 of 38 [47%], P < .001). MR showed higher sensitivity than did mammography for all tumor types (P < .01) and higher sensitivity than did US for DCIS (P < .001), depicting 105 of 110 (95%) cases of IDC, 28 of 29 (96%) cases of ILC, and 34 of 38 (89%) cases of DCIS. In anticipation of conservation or no surgery after mammography and clinical examination in 96 breasts, additional tumor (which altered surgical approach) was present in 30. Additional tumor was depicted in 17 of 96 (18%) breasts at US and in 29 of 96 (30%) at MR, though extent was now overestimated in 12 of 96 (12%) at US and 20 of 96 (21%) at MR imaging. After combined mammography, clinical examination, and US, MR depicted additional tumor in another 12 of 96 (12%) breasts and led to overestimation of extent in another six (6%); US showed no detection benefit after MR imaging. Bilateral cancer was present in 10 of 111 (9%) patients; contralateral tumor was depicted mammographically in six and with both US and MR in an additional three. One contralateral cancer was demonstrated only clinically. In nonfatty breasts, US and MR imaging were more sensitive than mammography for invasive cancer, but both MR imaging and US involved risk of overestimation of tumor extent. Combined mammography, clinical examination, and MR imaging were more sensitive than any other individual test or combination of tests. (c) RSNA, 2004.