Varanus prisca shares numerous features in common with Komodo dragons, especially in the detailed structure of the skull. These two animals are also closely related to the lace monitor (Varanus varius) and the water monitor (Varanus salvator). All of these species are known from Australia or South-East Asia and represent a radiation of large-bodied lizards from this region.
Other, more distantly related, large-bodied monitor lizards are known from Africa (e.g., the Nile monitor, Varanus niloticus) and Australia (the perentie, Varanus giganteus).
The evolutionary tree of these animals indicates that the evolution of large body size must have occurred on three separate occasions among monitor lizards.
Previously, it was argued that the large body size of Komodo dragons might have been related to living on islands, but their close relationship to Varanus prisca suggests that large body size was a feature already in place at the time Komodo was isolated from the rest of Indonesia and that these gigantic lizards may have moved back and forth between Australia and the Indonesian archipelago as sea-levels rose and fell.