ABSTRACT. The expressions of cytokeratin 8 and 18 (CK8 and CK18) in the normal canine skin (2 cases) and cutaneous adnexal tumors (127 cases) were investigated immunohistochemically. In the normal skin, co-expression of CK8/18 was found in the glandular epithelium of apocrine sweat glands, and single CK8-immunoreactivity was detected occasionally in the external root sheath at the isthmus and suprabulbar regions of the hair follicles. Neoplastic glandular epithelial cells in all apocrine gland tumors (21/21 cases, 100%) had co-expression of CK8/18. In trichoblastomas (27/28 cases, 96%), most neoplastic cells were diffusely positive for CK8, but those were negative for CK18. Single CK8-expression was also observed in basaloid neoplastic cells in several cases of trichoepitheliomas (7/19 cases, 37%) and pilomatricoma (1/7 cases, 14%). In several cases of trichoblastomas (4/28 cases, 14%) and trichoepitheliomas (2/19 cases, 11%), tumor cells forming glandular structures had co-expression of CK8/18. There were no positive reactions for both CK8 and 18 in infundibular keratinizing acanthomas, and sebaceous and hepatoid gland tumors. The present findings indicate that co-expression of CK8/18 is a specific feature of apocrine sweat glands and single CK8-expression represents the natures of external root sheath or pluripotential stem cells. Thus, the combination of CK8-and 18-immunostainings may have the utility to confirm the directions of differentiation in canine cutaneous adnexal tumors providing a reliable hallmark for histopathological diagnoses. The development of adnexa is result of an intimate interaction between basal and mesenchymal cells. Basal cells become the germinative cells of the hair follicle and mecenchymal cells become follicular papilla. Follicular stem cells are predominantly considered to be located in the specific region of the external root sheath, especially the bulge region, and are capable to give rise to the hair follicles, epidermis, sebaceous glands, and apocrine sweat glands [4]. Trichoblastoma is considered as benign tumor of hair germ cells. Most cases of basal cell tumors previously diagnosed in the domestic animals have been reclassified into trichoblastomas.Adnexal neoplasms sometimes have complex histological appearances because of their origin of the pluripotent stem cells. In human, several cases of trichoblastic tumors including trichoblastomas and trichoepitheliomas with complex adnexal differentiations such as apocrine sweat or sebaceous glands were reported [1, 5, 11, 13, 16-18, 20, 23, 26]. Canine adnexal tumors also have similar complex morphological natures, sometimes resulting in confused pathological diagnoses. To determine the useful diagnostic markers and evaluate the directions of differentiation in cutaneous adnexal tumors, several immunohistochemical analyses including cytokeratins (CKs) have been documented in humans [7,15,24,25]. CK8 and 18 are the intermediate filaments of single layer epithelium. CK8 and 18 were generally co-expressed in the glandular epithelium...