A diagnosis supporting system acquires a reference image signal of a subject illuminated with visible light and a fluorescent image signal of the subject excited by irradiation with excitation light. The diagnosis supporting system calculates a difference between a brightness level of a pixel in the reference image signal and a brightness level of a pixel in the fluorescent image signal at the corresponding position for target pixels. An observation image signal is generated by converting the pixels in the reference image signal with differences larger than a predetermined value into red pixels. In the case a ratio of the red pixels in the observation image signal is higher than a predetermined level, more pixels become the target pixels to be processed than in the other case.