Cutaneous hyperkeratosis is one of the many clinicopathological manifestations of canine distemper and is characterized by thickening and hardening of the skin, predominantly in nasodigital areas. Although this lesion may rarely affect other regions, this has been poorly characterized. Twelve dogs with canine distemper and cutaneous hyperkeratosis, necropsied at an anatomical pathology service, were investigated. Twenty-two cutaneous hyperkeratotic foci were observed on footpads (11/22), nasal planum (3/22), haired skin on the snout (2/22), periocular region (2/22), ventral abdomen (2/22), scrotum (1/22) and vulva (1/22). The dogs had one (5/12), two (4/12) or three (3/12) regions concomitantly affected. Orthokeratotic hyperkeratosis was a predominant histopathological feature in 17 dogs, occasionally accompanied by other lesions, including inclusion bodies (14/17), epidermal hyperplasia (9/17) and keratinocyte hydropic degeneration (6/17). Canine distemper virus antigen was expressed in at least one skin lesion in 10 dogs. Fourteen (14/17) hyperkeratotic foci were immunopositive while three (3/17) were immunonegative. Viral antigen expression was most common in the sweat glands (13/17), epidermis (11/17) and vascular endothelial cells or pericytes (8/17). Histological findings and antigen detection were similar among nasodigital and other regions. We emphasize the importance of clinicopathological recognition of these lesions for the initial suspicion of canine distemper, thereby facilitating early treatment.