Phylogenetic profiling encompasses an important set of methodologies for in silico high throughput inference of functional relationships between genes. The simplest profiles represent the distribution of gene presence-absence in a set of species as a sequence of 0s and 1s, and it is assumed that functionally related genes will have more similar profiles. The methodology has been successfully used in numerous studies of prokaryotic genomes, although its application in eukaryotes appears problematic, with reported low accuracy due to the complex genomic organization within this domain of life. Recently some groups have proposed an alternative approach based on the correlation of homologous gene group sizes, taking into account all potentially informative genetic events leading to a change in group size, regardless of whether they result in a de novo group gain or total gene group loss.