Widely accepted major criteria for biodiversity hotspots that deserve conservation include species richness, endemism and threat. Proving that a taxon is endemic to a given area is more difficult, and therefore expensive, with animals than with plants because of the difficulty to prove absence outside the known distribution. Seeking a cost-efficient practical method to show animal endemism while funds necessary for conventional demonstration of endemism are lacking, we argued that when the known distribution of a suspected endemic taxon coincides with an ecogeographically isolated area, e.g. island, its exclusivity to that area is more credible. We selected a model site containing suspected endemics, the 'Arava depression (altitude -400-0 m) between arid southern Israel and southern Jordan. A search of the literature and collections found at least 23 animal taxa endemic to the 'Arava, to the adjacent Dead Sea basin sharing the depression, or to both. We assessed the level of isolation of the 'Arava depression by statistically analysing the geographical distribution of taxa (species or subspecies) of one selected well researched model group, Squamata (lizards and snakes). In northern Israel and Jordan the squamate faunas of the two countries are very similar. In contrast in the south where the 'Arava intervenes, the two faunas greatly differ. The 'Arava both constitutes a partial barrier and is partly isolated. Hence its apparent endemics are likely real endemics, inviting conservation of the area. The more so since the 'Arava is also an arena of much research and education. Our methodology may serve worldwide to identify semi-isolated terrestrial areas for conservation.