The phylogeny of snakes is poorly known due to the fact that snake skeletons are typically small and fragile, making fossilization unlikely. It has however been generally agreed, on the basis of morphology, that snakes descended from lizard-like ancestors. Recent research based on genetics and biochemistry confirms this; snakes form a venom clade with several extant lizard families.
Morphology further suggests that the likeliest ancestors were related to mosasaurs — extinct aquatic reptiles from the Cretaceous — which in turn are thought to have derived from varanid lizards. Under this hypothesis, the fused, transparent eyelids of snakes are thought to have evolved to combat marine conditions (corneal water loss through osmosis), while the external ears were lost through disuse in an aquatic environment, ultimately leading to an animal similar in appearance to sea snakes of today. In the Late Cretaceous, snakes re-colonized the land much like they are today. The best fossil snake remains are from Late Cretateous marine sediments, which supports this hypothesis. Similar skull structure; reduced/absent limbs; and other anatomical features found in both mosasaurs and snakes lead to a positive cladistical correlation, though some features are also shared with varanids. Supposedly similar locomotion for both groups is also used as support for this hypothesis.
An alternative hypothesis is that snakes directly evolved from burrowing lizards, either varanids or some other group. One extant analog of these putative ancestors is the earless monitor Lanthanotus of Borneo, although it also is semi-aquatic. As these ancestors became more subterranean, they lost their limbs and became more streamlined for burrowing. Features such as the transparent, fused eyelids and loss of external ears, according to this hypothesis, evolved to combat subterranean conditions (scratched corneas, dirt in the ears). As with the marine origin hypothesis, snakes re-emerged onto the surface of the land much as they are today. Fragmentary remains that have been found from the Early Cretaceous may refute either hypothesis. Further insight will no doubt also come from more detailed genetic studies.
The great diversity of modern snakes appeared in the Paleocene, probably correlated with the adaptive radiation of mammals following the extinction of the dinosaurs.