The purpose of this study was to examine the role of sonography in the evaluation of a focal asymmetric density of the breast in patients who subsequently underwent biopsy for this finding. During a 30-month period, the clinical, sonographic, and pathologic findings were retrospectively reviewed in 36 women who underwent biopsy for a focal asymmetric density of the breast after mammographic and sonographic workup. Sonographic evaluation of a focal asymmetric density of the breast in 36 women demonstrated a solid mass in 15, a suspected complicated cyst in two, echogenic tissue in nine women, and no focal sonographic change in 10. Excisional biopsy of the focal asymmetric density revealed infiltrating ductal cancer in seven patients (19.4%: 7/36). Two of these seven patients with breast cancer had no focal abnormality at sonographic examination. Twenty-nine patients had benign pathologic findings. In this retrospective study, the negative predictive value of sonography for breast cancer in a patient with a focal asymmetric density undergoing biopsy was found to be 89.4% (17/19). Sonographic evaluation of a focal asymmetric density is helpful, particularly to identify an underlying mass. When sonography demonstrates echogenic tissue corresponding to the focal asymmetric density, a benign process is likely; however, absence of a corresponding focal finding does not exclude malignancy. Therefore, although the negative predictive value of sonography for breast cancer in a patient with a focal asymmetric density is high, biopsy is still indicated for this mammographic finding when it is new, enlarging, or palpable, even in the absence of a suspicious sonographic finding.