A prospective study was undertaken to evaluate the significance of asymmetric breast tissue (asymmetric volume of breast tissue, asymmetrically dense breast tissue with preserved architecture, or asymmetrically prominent ducts) on mammograms. Of 8,408 mammograms obtained in 1985, 221 (3%) demonstrated asymmetric breast tissue. Follow-up was 36-42 months after the initial mammographic study. During this time none of the patients underwent biopsy on the basis of mammographic findings, although 20 underwent excisional biopsy because of clinical findings. Breast cancer was diagnosed in two patients and breast lymphoma in one patient. Biopsy specimens from the remaining 17 patients were benign. At mammography, all three malignant lesions had a palpable abnormality associated with the asymmetric tissue. Breast cancer was not found in any of the remaining 201 patients. Therefore, an asymmetric volume of breast tissue, asymmetrically dense breast tissue, or asymmetrically prominent ducts that do not form a mass, do not contain microcalcifications, or do not produce architectural distortion should be viewed with concern only when associated with a palpable asymmetry and are otherwise normal variations.