The purpose of this study was to determine how often physician-performed high-resolution sonography can detect nonpalpable breast lesions not revealed by mammography. A sonographic classification scheme was tested for its accuracy in predicting malignancy of incidentally detected breast lesions. Six thousand one hundred thirteen asymptomatic women with breast density grades 2-4 and 687 patients with palpable or mammographically detected breast masses underwent sonography as an adjunct to mammography. All sonographically detected, clinically and mammographically occult breast lesions that were not simple cysts were prospectively classified into benign, indeterminate, or malignant categories. Diagnoses were confirmed by sonographically guided fine-needle aspiration or core needle biopsy. In 6113 asymptomatic women, 23 malignancies in 21 patients were detected with sonography only (prevalence, 0.31%). Five additional malignant lesions were found in patients with a malignant (n = 3) or a benign (n = 2) palpable or mammographically detected index lesion. The mean size of invasive malignancies detected only by sonography was 9.1 mm, which was not significantly different from the mean size of invasive cancers detected by mammography (p = .07). The sensitivity of the prospective sonographic classification for malignancy was 100%, and the specificity was 33.5%. The use of high-resolution sonography as an adjunct to mammography in women with dense breasts may lead to detection of a significant number of otherwise occult malignancies that are no different in size from nonpalpable mammographically detected lesions. Prospective classification of these lesions based on sonographic characteristics results in a significant reduction in number of unnecessary biopsies performed.