Eukaryotic genomes are compositionally heterogeneous, that is, composed by regions that differ in guanine–cytosine (GC) content (isochores). The most well documented case is that of vertebrates (mainly mammals) although it has been also noted among unicellular eukaryotes and invertebrates. In the human genome, regarded as a typical mammal, this heterogeneity is associated with several features. Specifically, genes located in GC-richest regions are the GC3-richest, display CpG islands and have shorter introns. Furthermore, these genes are more heavily expressed and tend to be located at the extremes of the chromosomes. Although the compositional heterogeneity seems to be widespread among eukaryotes, the associated properties noted in the human genome and other mammals have not been investigated in depth in other taxa. Here we provide evidence that the genome of the parasitic flatworm Schistosoma mansoni is compositionally heterogeneous and exhibits an isochore-like structure, displaying some features associated, until now, only with the human and other vertebrate genomes, with the exception of gene concentration.