In January 2010, 18 months after excision of an ocular squamous cell carcinoma (SCC), a Connemara mare presented with anorexia and periorbital/parotideal lesions. Post mortem examination revealed these lesions as forming one entity, with 2 additional growths in the retropharyngeal region and the left jugular groove, respectively. The lesions were confirmed histopathologically as SCCs. Using PCR, peripheral blood mononuclear cells (PBMCs) from 2008 and 2010, tumour tissue, intact skin and vulval mucosa were screened for Equus caballus papillomavirus type 2 (EcPV-2) and bovine papillomavirus types 1 and 2 (BPV-1/2) DNA. Whereas PBMCs from 2008 scored negative, EcPV-2 DNA was present in PBMCs and SCCs from 2010. Furthermore, reverse transcription PCR revealed EcPV-2 E6 transcripts in these samples. BPV-1/2 DNA, but not RNA, was demonstrated in the periorbital/parotideal mass, the SCC of the jugular groove, vulval mucosa and intact skin, but not in the pharyngeal SCC and PBMCs. Sequencing revealed a 99% similarity of EcPV-2 amplicons with the published EcPV-2 sequence. BPV-1/2 amplicons corresponded to BPV type 1. This report is the first to describe co-presence of BPV-1 and EcPV-2 DNA in a pony affected by an uncommon form of nongenital SCC, and the detection of EcPV-2 transcripts in lesions and PBMCs.