ABSTRACT. The bovine papillomavirus (BPV) causes papillomas that regress spontaneously, but can also progress to malignancy. This study evaluated the role of BPV in oncogenesis. Twenty-four samples from uninfected calves and the papillomas of BPV infected cattle were subjected to molecular diagnosis, as well as histopathological and immunohistochemical analyses. The comet assay (CA) was used to evaluate the clastogenic potential of BPV. The results confirmed the presence of BPV-2, 3, 5, and 9 in infected samples. Histopathological analysis revealed acanthosis, koilocytosis, hypergranulosis, hyperkeratosis, and transformed fibroblasts. E7 and L1 BPV proteins were detected in the epithelium, as well as in the connective tissues, indicating productive infection at different sites. CA 12943 Genetics and histopathological aspects of BPV ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 12942-12954 (2015) results showed that BPV-2, 5, and 9 exhibit the same level of clastogenicity. These findings support the oncogenic action of BPV in establishing a favorable microenvironment for oncogenesis.