In this paper, a complete study of automatizing the manipulation process of tanned natural leather plies is presented. The considered leather plies are partially refined and their surface is suitable for grasping by suction grippers. The particular features (non-rigid structure, irregular shape and size, etc.) of such a material make the handling and loading on the workstations very critical and difficult to be approached. To increase the reliability of grasping, the development of customized vacuum cups seems to be advisable. In the paper, an innovative vacuum cup model is proposed. Its performances are quantitatively compared with a other models by means of appropriate measuring methods. Another problem concerning the automatic manipulation of leather plies is to avoid the grasping of more than one ply at a time, due to the irregularity of the ply profile. A device able to solve this problem, using an innovative equipment for moving the entire stack from the store to the workstation and for separating the plies, is also shown and discussed.