e papilloma viruses are constituted of double-stranded DNA and are a more common lesion in ruminant's skin in Iraq. e p53 tumor suppressor protein reveals an essential role in cell cycle control. is study intends to investigate the clinical, histopathological, and immunohistochemical features of cutaneous papilloma in ruminants in Iraq. Samples had been collected from a total of 10 animals (three cattle, three goats, and four sheep) with multiple papillomatosis lesions. e samples were processed for histopathological and immunohistochemical techniques. Clinically, the lesions appeared as multiple various sizes (0.5-11 cm), cauliflower exophytic masses on different parts of the animal's body. e histopathological features of the epidermis granular layer revealed perinuclear vacuolation (koilocytosis) accompanied by various degrees of hypergranulosis, hyperkeratosis, acanthosis, orthokeratosis, and parakeratosis. Strong positive reaction for papillomavirus antigen was seen in both epidermal basal and granular layers in the immunohistochemical investigation (IHC). Moreover, all papilloma lesions revealed an intense positive p53 reaction in cytoplasmic and perinuclear of the basal and parabasal layers. In conclusion, this study described the papillomavirus lesions in bovine, ovine, and caprine animals, which were found in different parts areas of the affected animals. All lesions show similar histopathological features with minor variations. PV antigen and p53 protein expression showed positive results in immunohistochemistry that can be used as diagnostic markers for ruminant's papilloma.