Background: Papillomaviruses (PVs) are double-stranded DNA viruses and are more common in skin of ruminants in Iraq. A P53 (tumor suppressor protein) reveals an essential role in cell cycle control. This study aimed to describe the clinical, histopathological and immunohistochemical aspects of naturally occurring cutaneous ruminant’s papillomatosis. Methods: Samples were collected from totally, 10 animals (3 cattle, 3 goats and 4 sheep) with multiple papillomatosis lesions. Results: Clinically, exophytic multiple, cauliflower-like growths (warts) of varying sizes (0.5-11 cm) were found in different areas of the animal’s bodies. Histopathological features were various degrees of koilocytosis, ortho and parakeratotic, hyperkeratosis, hypergranulosis in granular layer and acanthosis. Immunohistochemical (IHC) investigations revealed some nuclei in the granular and basal layers of the epidermis with intense positivity for papillomavirus antigen. All tumor samples were positive for p53 expression that appeared as a strong cytoplasmic and perinuclear staining mainly in the basal and parabasal layers. Conclusion: this study described the papillomavirus lesions in bovine, ovine and caprine, that located in different anatomical areas with minor variations in histopathological features. The tumor samples showed positive results for PV antigen and P53 expression that considered as the useful markers in the diagnosis of cutaneous papilloma.