Provided are a processor device, an endoscope system, and a method of operating the processor device capable of distinguishing respective tissues included in an observation target. A Bs image signal, a Gs image signal, and an Rs image signal obtained by imaging the observation target including at least one tissue are acquired. A calculated image is obtained by performing specific calculation processing on the basis of these images of bands. The tissue discrimination unit 74 discriminates the tissue on the basis of a brightness value of the Bs image signal and the calculated image.