This study examined whether a specific (six-nucleotide) sequence in the norovirus polymerase (POL) gene could act as a marker of GII.4 epidemics in Australia in 2001-2005. The predominant variant (pv) in an epidemic year (2002, 2004) changed relative to the pv in the previous year (AACTTG in 2001 to AATCTG in 2002, AATCTG in 2003 to AACTTG in 2004). The pv in a non-epidemic year (2003, 2005) was the same as in the preceding year (AATCTG in 2002 and 2003, AACTTG in 2004 and 2005). Thus, specific short nucleotide sequences could act as markers of major GII.4 norovirus epidemics.