Cross–species painting (fluorescence in situ hybridization) with 23 (human Homo sapiens (HSA)) chromosome–specific painting probes (HSA 1–22 and the X) was used to delimit regions of homology on the chromosomes of the golden mole (Chrysochloris asiaticus) and elephant–shrew (Elephantulus rupestris). A cladistic interpretation of our data provides evidence of two unique associations, HSA 1/19p and 5/21/3, that support Afrotheria. The recognition of HSA 5/3/21 expands on the 3/21 synteny originally designated as an ancestral state for all eutherians. We have identified one adjacent segment combination (HSA2/8p/4) that is supportive of Afroinsectiphillia (aardvark, golden mole, elephant–shrew). Two segmental combinations (HSA 10q/17 and HSA 3/20) unite the aardvark and elephant–shrews as sister taxa. The finding that segmental syntenies in evolutionarily distant taxa can improve phylogenetic resolution suggests that they may be useful for testing sequence–based phylogenies of the early eutherian mammals. They may even suggest clades that sequence trees are not recovering with any consistency and thus encourage the search for additional rare genomic changes among afrotheres.