For eukaryotes, synthetic biologists have created individual genes or pathways but not entire genomes. Dymond et al. take a step towards achieving the latter with a paper in Nature that describes the first synthetic eukaryotic chromosome arm, the 90-kb right arm of chromosome IX in the yeast Saccharomyces cerevisiae. In terms of sheer numbers of base pairs, this DNA molecule is smaller than the 1.08-Mb synthetic prokaryotic genome recently reported, but it was designed with several notable features, including the recoding of all instances of one stop codon to support an expanded genetic code, the addition of unique sequence tags that identify the synthetic DNA, the removal of destabilizing DNA sequences and the strategic scattering of 43 loxP recombination sites throughout the chromosome arm. Synthesis of the DNA itself was reported in Nucleic Acids Research last year. Dymond et al. show that transient expression of the Cre recombinase resulted in extensive deletions and inversions between the loxP sites, generating strain libraries from which auxotrophic mutants could be recovered. (Nature 477, 471–476, 2011; Nucleic. Acids Res. 38, 2594–2602, 2010)