Collagenous spherulosis of the breast is a recently described benign breast lesion that has previously been seen only incidentally. The authors report two cases of this lesion studied by immunohistochemistry and electron microscopy and a third case studied by light microscopy alone. The results demonstrate the participation of two cell types in the process: myoepithelial cells, which stained positively for cytokeratin, S-100 protein, and muscle-specific actin and contained intermediate filaments with dense bodies, pinocytotic vesicles, and formed cell junctions; and epithelial cells, which reacted for cytokeratin but not for S-100 protein or muscle-specific actin and contained intracytoplasmic lumina, formed lumina with microvilli, and desmosomes. Material constituting the spherules stained intensely for type IV collagen, and its ultrastructure was similar to that of basement-membrane material. The authors conclude that collagenous spherulosis results from a proliferation of epithelial and myoepithelial cells, the latter of which produce basement-membrane material.