Dengue virus type 3 genotype III (DENV-3/III) is widely distributed in most dengue-endemic regions. It emerged in Malaysia in 2008 and autochthonously spread in the midst of endemic DENV-3/I circulation. The spread, however, was limited and the virus did not cause any major outbreak. Spatiotemporal distribution study of DENV-3 over the period between 2005 and 2011 revealed that dengue cases involving DENV-3/III occurred mostly in areas without pre-existing circulating DENV-3. Neutralisation assays performed using sera of patients with the respective infection showed that the DENV-3/III viruses can be effectively neutralised by sera of patients with DENV-3 infection (50% foci reduction neutralisation titres (FRNT50) > 1300). Sera of patients with DENV-1 infection (FRNT50 ⩾ 190), but not sera of patients with DENV-2 infection (FRNT50 ⩽ 50), were also able to neutralise the virus. These findings highlight the possibility that the pre-existing homotypic DENV-3 and the cross-reacting heterotypic DENV-1 antibody responses could play a role in mitigating a major outbreak involving DENV-3/III in the Klang Valley, Malaysia.