The reduction or loss of E-cadherin (E-cad), a calcium-dependent epithelial cell adhesion molecule, has been associated with tumor dedifferentiation and invasiveness. The immunohistochemical pattern of E-cad expression was evaluated in formalin-fixed and paraffin-embedded sections of 6 normal mammary glands, 3 dysplasias, 12 benign tumors (8 benign mixed tumors, 4 adenomas), and 60 malignant tumors (12 stage 0, 29 stage I, 19 stage II) of the canine mammary gland. E-cadherin expression was classified as membranous, when on cell-cell boundaries, or as cytoplasmic, when in the form of a diffuse cytoplasmic staining. In addition, the percentage of E-cad-positive epithelial neoplastic cells was graded by a semiquantitative method, categorizing cases into a reduced (or -) type group, when showing less than 25% positivity, a reduced (or +/-) type group, when showing 25-75% positivity, and a preserved (or +) type group, when more than 75% positive cells were present. In the normal mammary gland, E-cad expression was evident in epithelial luminal cells. A stronger positivity was revealed in ductular than in alveolar luminal cells. The myoepithelial cells showed inconsistent, weak cytoplasmic positivity in the normal gland as well as in mammary tumors. In normal glands and benign and malignant noninvasive tumors, E-cad expression was mainly membranous and preserved in most of the epithelial cells. In stage I tumors, both membranous (38%) and cytoplasmic (62%) positivity were well represented, as well as preserved type (55%) and reduced type (45%) tumors. All stage II malignant tumors showed the highest frequency of cytoplasmic positivity (79%) and reduced type (62%) tumors.