The present report describes the peptide commonality between JC virus (JCV) and the human proteome at the heptamer level. In total, 53 viral heptapeptides occur in functionally important human proteins with potential consequences for host functions and JCV pathogenesis. A paradigmatic example of a crucial peptide match is the SGKTTLA sequence, shared by JCV LT antigen and human nicotinamide/nicotinic acid riboside kinase, an enzyme involved in myelination processes. In general, the JCV-versus-host heptapeptide overlap may result in a competition between viral sequences and identical motifs in host enzymic active sites, adhesive domains, regulatory signaling motifs, etc., thus interfering with essential reactions and posing disadvantages to the cell. Overall, this study provides a starting point for investigating the role of peptide commonality in host-pathogen interactions.