In this report, a fast and straightforward approach for the construction of chimeric (flavi)viruses is reported. Instead of three amplification reactions with four primers as used in a ‘classical fusion reaction’, a fusion between two different genes is accomplished by only two amplification reactions (and the use of three primers), thereby reducing the risk of accumulating mutations. This strategy was employed to construct a Modoc/YF chimeric virus. YF-17D was used as a backbone in which the prM+E proteins were exchanged with those of Modoc virus (MOD), a flavivirus with no known vector that causes lethal encephalitis in mice and hamsters (Leyssen et al., 2001 and Leyssen et al., 2002).