ABSTRACT: A novel papillomavirus (PV) associated with hyperplastic nodules scattered over the muco-cutaneous border of the oral cavity of a dead, wild, subadult northern sea otter Enhydra lutris kenyoni (NSO) in 2004 in Homer, Alaska, USA, was genetically characterized. Primers for the amplification of 2 large overlapping DNA fragments that contained the complete genome of the NSO PV were designed. Sanger methodology generated sequences from which new specific primers were designed for the primer-walking approach. The NSO PV genome consists of 8085 nucleotides and contains an early region composed of E6, E7, E1, and E2 open reading frames (ORFs), an E4 ORF (contained within E2) lacking an in-frame proximal ATG start codon, an unusually long (907 nucleotide) stretch lacking any ORFs, a late region that contains the capsid genes L2 and L1, and a non-coding regulatory region (ncRR). This NSO PV has been tentatively named Enhydra lutris kenyoni PV2 (ElkPV2). Pairwise and multiple sequence alignments of the complete L1 ORF nucleotides and concatenated E1-E2-L1 amino acid sequences showed that the NSO PV is a novel PV, phylogenetically most closely related to southern sea otter PV1. The carboxy end of the E6 oncoprotein does not contain the PDZ-binding motif with a strong correlation with oncogenicity, suggesting a low-risk PV, which is in agreement with histopathological findings. However, the ElkPV2 E7 oncoprotein does contain the retinoblastoma (pRb) binding domain LXCXE (LQCYE in ElkPV2), associated with oncogenicity in some high-risk PVs. Further studies on the prevalence and clinical significance of ElkPV2 infections in NSO are needed.