It is well-known that malfunctioning of the phototransduction mechanism stimulates the cell death machinery, resulting in retinal degeneration both in vertebrates and invertebrates. Genetic screens have often failed to identify modifiers underlying such degenerative syndromes because of the lethality associated with their fundamental function during development. A norpA P24 suppressor screen was successful performed with mosaic flies generated by the yeast site-specific recombination FLP-FRT system. Three independent diehard mutants, identified by mutagenizing the 2L FRT chromosome in the norpA P24 background, include both essential and non-essential mutations. Their suppressive effects on the norpA P24 -triggered retinal degeneration depend on the intensity and duration of light based on a deep pseudopupil analysis and histology. These results suggest that the suppressor screen using mosaic flies provides a valuable tool for recovering both essential and non-essential genes within the fundamental genetic pathways. Further studies of diehard mutants will provide insights into the disease mechanism that underlies the retinal degeneration of phototransduction mutants.