Objective To perform phylogenetic study on the flamingo cadherin subfamily and explore the evolutionary differences between the flamingo cadherins of vertebrates and those of invertebrate. Methods Phylogenetic trees were established, the protein domains were compareds and the gene structure analyses was conducted. Results The flamingo cadherin subfamily was originated from eumetazoa. In vertebrates,two duplication events occurred and resulted in the three paralogs. Intron insertions were found in the vertebrate flamingo protein domains, and two highly conserved motifs were also showed in the vertebrate flamingo cytoplasm. Both of them can be viewed as the evolutionary characteristics of vertebrate flamingo cytoplasm. Conclusion There are significant evolutionary differences between the flamingo cadheins of vertebrates and those of invertebrates. Together with the positioning information that the Celsr1 gene,one of the mouse flamingo paralogs,is located in the quantiative trait loci(QTL) which is related to mice spinal cord development, Celsr1 can be considered as a candidate gene of mice spinal cord development for further studies.