In Drosophila, Black cells (Bc) encodes a Prophenoloxidase and is expressed late in the maturation of crystal cells, which are blood cells involved in wound healing and immune encapsulation. Enhancer analysis of Bc revealed a 1,025-bp upstream sequence that regulates gene expression in a crystal cell exclusive pattern. Expression of this fragment is altered by mutations in the GATA family serpent (srp) and RUNX family lozenge (lz) genes; Srp and Lz are required for crystal cell specification. Deletional analysis uncovered a 330-bp crystal cell-specific sequence, which contains two GATA and three Lz binding sites. Mutational analysis revealed that both GATA sites are necessary, but not sufficient for crystal cell expression. However, one of the Lz sites is essential for crystal cell expression. Thus, Srp and Lz do not just specify the crystal cell lineage, but also regulate the later differentiation of these cells. Additionally, we now have a sensitive tool for marking crystal cells in live animals.