Disclosed are a medical image processing device for generating an image in which a difference in color between an abnormal part, such as an atrophic part where a gastric mucosa is atrophied, and a normal part is enhanced, an operation method therefore, and an endoscope system. RGB image signals are input. A B/G ratio is determined from the B image signal and the G image signal, and a G/R ratio is determined from the G image signal and the R image signal. In a feature space formed from the B/G ratio and the G/R ratio, first processing is performed for moving the coordinates of a second range to a reference range including the origin in a state where the coordinates of first and third ranges are maintained. In order to make the coordinates of the first range and the coordinates of the third range distant from each other, second processing is performed for moving the coordinates of the first range and the coordinates of the third range. A first special image is generated based on the B/G ratio and the G/R ratio after the first and second processing.