Disclosed is a diagnosis supporting system that acquires a reference image signal of a subject that is illuminated with visible light and a fluorescent image signal of the subject that is excited by irradiation with excitation light, calculates a difference between brightness level of a pixel in the reference image signal and brightness level of a pixel in the fluorescent image signal at the corresponding position for all of target pixels and generates an observation image signal by converting the pixels in the reference image signal whose differences are larger than a predetermined value into red pixels. In the case of high contrast, all of the pixels become target pixels to be processed. In the case of low contrast, the number of the target pixels is reduced to 1/4 of all the pixels.