Fifteen examples of a hitherto undescribed lesion, which we have designated “collagenous spherulosis”, were encountered in breast tissue from women aged 39 to 55 years. The lesion, which was multifocal in eight cases, was an incidental microscopic finding involving lobular acini and ductules, and consisted of intraluminal clusters of eosinophilic spherules measuring approximately 20-100 µ in diameter. The spherules typically were found, and appeared to originate, within the spaces of fenestrated epitheliosis (“papillomatosis”). Special stains indicated that the spherules were collagen–rich, but also contained variable amounts of acidic mucin, PAS–positive, basement membrane–like material, and elastin. With immunoperoxidase staining, the cells immediately surrounding the spherules stained positively for actin, suggesting myoepithelial differentiation. Collagenous spherulosis was typically situated adjacent to, or encompassed by, other benign proliferative processes, including intraductal papillomas, sclerosing adenosis, and “infiltrating epitheliosis” (radial scars). Collagenous spherulosis is a clinically and histologically benign lesion that on microscopic examination has been confused with—and should be distinguished from—malignant lesions including adenoid cystic carcinoma of the breast and socalled intraductal signet-ring carcinoma.