We are using image systems simulation technology to design a digital camera for measuring fluorescent signals; a first application is oral cancer screening. We validate the simulations by creating a camera model that accurately predicts measured RGB values for any spectral radiance. Then we use the excitationemission spectra for different biological fluorophores to predict measurements of fluorescence of oral mucosal tissue under several different illuminations. The simulations and measurements are useful for (a) designing cameras that measure tissue fluorescence and (b) clarifying which fluorophores may be diagnostic in identifying precancerous tissue.