The serine integrases have recently emerged as powerful new chromosome engineering tools in various organisms and show promise for therapeutic use in human cells. The serine integrases are structurally and mechanistically unrelated to the bacteriophage λ integrase but share a similar catalytic domain with the resolvase/invertase enzymes typified by the resolvase proteins from transposons Tn3 and γδ. Here we report the crystal structure and solution properties of the catalytic domain from bacteriophage TP901-1 integrase. The protein is a dimer in solution but crystallizes as a tetramer that is closely related in overall architecture to structures of activated γδ-resolvase mutants. The ability of the integrase tetramer to explain biochemical experiments performed in the resolvase and invertase systems suggests that the TP901 integrase tetramer represents a unique intermediate on the recombination pathway that is shared within the serine recombinase superfamily.