The composition of the mineralized matrix of the calcifying epithelioma of Malherbe (pilomatrixoma) and the process of mineralization have been investigated in two different tumors, one largely calcified and the other only slightly calcified. Fractionation of the tissue has been performed by isopycnic centrifugation. Whatever the mineral content of the fractions, their matrix is composed of a small proportion of collagen and a large proportion of keratin. The amino acid composition of this keratin is closer to that of nail than of hair. The hydroxylapatite crystals are associated with the keratin and the process of mineralization is accompanied by a progressive reduction in this polypeptide matrix. The chemical composition of this keratin, the known examples of calcification of hard keratin and the analogy of the ultrastructural pathways in the keratinization of pilomatrixoma and nails, suggest that the pilomatrixoma arises from the differentiation of ectopic ectodermal cells under the influence of an inducing system similar to that of nail.