An image processing device that enhances changes in color of mucosa or the like that may occur at the time of atrophy of stomach due to atrophic gastritis and a method for operating an endoscope system are provided.A first signal ratio (-log(B/G)) between a B image signal and a G image signal is calculated. A second signal ratio (-log(G/R)) between the G image signal and an R image signal is calculated. A difference between first and second signal ratios in a first area and first and second signal ratios in a specific area is increased to enhance a color difference between normal mucosa and an abnormal region (an atrophic mucosal region and a deep blood vessel region). The color difference between the normal mucosa and the abnormal region in a case where at least one of the RGB image signals is a narrowband image signal is greater than the color difference in a case where all of the RGB image signals are broadband image signals.