We have identified a novel Drosophila Sox-domain gene, Sox100B, related to the vertebrate group E genes Sox9 and Sox10. In vertebrates, group E Sox genes are expressed in the developing gonad, adult kidney and gut as well as other tissues. During embryogenesis in Drosophila, Sox100B is expressed in two rows of large intestinal cells, in midgut basophilic cells, in the Malpighian tubules and at the posterior cap of gonadal mesoderm. Our observations indicate that aspects of tissue-specific expression, as well as sequence, are conserved between vertebrate and invertebrate group E Sox proteins.