Provided are a processor device, an endoscope system, and a method of operating a processor device capable of narrowing down a plurality of index values to the index value required to diagnose a lesion. An image obtained by imaging an observation target including a structure is acquired. An index value calculation unit 70 performs an index value calculation process of calculating a plurality of index values obtained by indexing a property of the structure on the basis of the image. An index value arithmetic processing unit 74 controls the index value calculation unit 70 according to a processing order in which a first index value is calculated and then a second index value different from the first index value is calculated among the plurality of index values.