Sequences of the nuclear gene C-mos from 16 new species have been combined with previously published data to produce an analysis of squamate relationships using 56 taxa, considerably more than in previous analyses. Support for many nodes is greatly increased, thus producing a more robust assessment of relationships. Sampling was concentrated within the families Iguanidae and Lacertidae, both of which have poorly supported phylogenies based on mtDNA sequence data. Our analysis supports a robust estimate of relationships within the Iguanidae. Within the Lacertidae relationships are only partially well resolved, and this provides independent evidence for rapid speciation within this family.