Aim: We explored the phylogenetic relationships of species of Mesalina, using one nuclear and two mitochondrial loci. This genus of lacertid lizards is widely distributed in North Africa and the Middle East and our goal was to develop a scenario capable of explaining the current distribution and evolutionary patterns within the genus in the context of the wider historical biogeography of the region. Location: North Africa and the Middle East. Methods: The assembled dataset consisted of 193 Mesalina individuals, representing 12 species distributed across the geographical range of the genus. Bayesian and maximum likelihood methods were used to support phylogenetic inferences on two mitochondrial (cytochrome b and 16S ribosomal RNA) and one nuclear (beta-fibrinogen intron 7) markers. Palaeogeographical and palaeoclimatic data were used to support the inferred phylogeographical patterns. Results: Mesalina lizards exhibit high genetic diversity and complex phylogenetic patterns, leading to an unsatisfactory systematic hypothesis of one paraphyletic and three polyphyletic traditional species. The estimated divergence times place the origin of the genus in the early Miocene (c. 22 Ma) and the divergence of most currently recognized species in the middle to late Miocene. The inferred ancestral distribution suggests that the genus and most of its species originated somewhere in Arabia or the Middle East, with the exception of the Mesalina olivieri complex, which may be of African origin. Main conclusions: Phylogenetic reconstruction based on the three loci studied suggests a higher than expected cryptic diversity of Mesalina in North Africa and the Middle East. We suggest that the tectonic movements of the Arabian plate, coupled with the climatic changes occurring since the Miocene, may be responsible for the phylogeographical patterns of North African and Middle Eastern Mesalina.