Noroviruses are considered the most common cause of outbreaks of non-bacterial gastroenteritis in humans and the GII.4 genotype the most common norovirus genotype. Previous studies have shown that two adjacent codons acted as markers of the severity of GII.4 norovirus outbreak epidemics. In this study, a further such codon was identified at nucleotide position 4670-4672 relative to the norovirus strain Lordsdale virus (GenBank accession no. X86557). Taken together, the data indicate these epidemic marker sites occur, on average, about once in 30 amino acids (aa) in the polymerase region. None of the variant forms associated with the three codons resulted in an aa change. The three codons were not associated with the active sites of the polymerase gene. It is possible changes in these marker sites may influence norovirus virulence by altering the timing of co-translational folding in the norovirus genome.