Ongoing surveillance detected a SARS-CoV-2 B.1.1.220 variant carrying the E484K substitution in four patients from a hospital network in upstate New York . Patients reported no travel history and shared no obvious epidemiological linkage . A search of online databases identified 12 additional B.1.1.220 with E484K, all of which were detected in New York since December 2020 . Detailed genomic analyses suggests that the mutation has emerged independently in at least two different B.1.1.220 strains in this region.