Gecko2 is a further development of the original Gecko software. It allows for the systematic detection of gene cluster conservation in a large number of genomes. The enhancement over the original Gecko tool is the use of set-distance based gene cluster models that allow for the detection of gene clusters with diverse conservation patterns including gaps and missing genes in cluster occurrences. It is also tolerant of errors in gene homology assignment. Gecko2 provides a ranking of the predictions based on statistical significance and an interactive visualization that supports the functional evaluation of the clustered genes.