Viral wildlife reservoirs can contribute to the evolution of SARS-CoV-2 variants and potentially the emergence of variants of concern. Spillback of such new variants to the human population has the potential to affect vaccine efficacy or disease severity. Evidence suggests the continual transmission of SARS-CoV-2 from humans to white-tailed deer, but so far, there was no evidence of transmission from deer to humans. Now, Pickering, Mubareka, Bowman and colleagues report the identification of a highly divergent lineage of SARS-CoV-2 in white-tailed deer (B.1.641) in an observational surveillance study in Ontario, Canada, during November and December 2021. This lineage is one of the most divergent lineages identified so far, and several of the mutations in the B.1.641 genomes have not been described previously, or are rare and uncharacterized. Phylogenetic analysis revealed that B.1.641 shares a common ancestor with mink- and human-derived viral sequences from a nearby area. The authors speculate that the viral ancestor of B.1.641 stems from an unknown animal or a human reservoir. Subsequently, there was either a spillback transmission from deer to human or the emergence of a virus that can infect both human and deer. Continued surveillance is critical to identify new intermediate or reservoir hosts that drive viral evolution and transmission.