Device for processing a biological sample hosted on a support, wherein said biological sample comprises at least one biological tissue included in a block of containment material, said device comprising: - an image acquisition system comprising an optical detector for acquiring at least one image of said biological sample, - an automated transport line comprising an automatic conveyor defining a transport surface on which the support of the biological sample is transported, in order to advance said support hosting the biological sample towards said image acquisition system, - an electronic processing unit associated with said image acquisition system and programmed to receive and process a first signal emitted by said optical detector and indicative of the acquired biological sample image, and - an electronic controller configured to receive a second signal emitted by said electronic processing unit, wherein: - the device further comprises an operator apparatus placed downstream of said image acquisition system, towards which said support hosting the biological sample is advanced by means of said transport line, said operator apparatus comprising at least one operating head which can be moved in a controlled way both along a plane xy parallel to said transport surface of the automatic conveyor, and along a z axis perpendicular to said transport surface of the automatic conveyor, - the electronic processing unit associated with said image acquisition system is programmed in such a way that said second signal is indicative of the position into space of at least a portion of said block of containment material where there is no biological tissue, and - said electronic controller is configured and programmed to control said operator apparatus on the basis of said second signal coming from said electronic processing unit to position the at least one operating head in correspondence with said portion of the block of containment material where there is no biological tissue and subsequently to make said operating head perform the following operations in that order: (a) removal of a predefined volume of the block of containment material in correspondence with said portion, and (b) insertion of at least one reference material in replacement of said volume of the block of containment material which has been removed. - an image acquisition system comprising an optical detector for acquiring at least one image of said biological sample, - an automated transport line comprising an automatic conveyor defining a transport surface on which the support of the biological sample is transported, in order to advance said support hosting the biological sample towards said image acquisition system, - an electronic processing unit associated with said image acquisition system and programmed to receive and process a first signal emitted by said optical detector and indicative of the acquired biological sample image, and - an electronic controller configured to receive a second signal emitted by said electronic processing unit, - the device further comprises an operator apparatus placed downstream of said image acquisition system, towards which said support hosting the biological sample is advanced by means of said transport line, said operator apparatus comprising at least one operating head which can be moved in a controlled way both along a plane xy parallel to said transport surface of the automatic conveyor, and along a z axis perpendicular to said transport surface of the automatic conveyor, - the electronic processing unit associated with said image acquisition system is programmed in such a way that said second signal is indicative of the position into space of at least a portion of said block of containment material where there is no biological tissue, and - said electronic controller is configured and programmed to control said operator apparatus on the basis of said second signal coming from said electronic processing unit to position the at least one operating head in correspondence with said portion of the block of containment material where there is no biological tissue and subsequently to make said operating head perform the following operations in that order: (a) removal of a predefined volume of the block of containment material in correspondence with said portion, and (b) insertion of at least one reference material in replacement of said volume of the block of containment material which has been removed. (a) removal of a predefined volume of the block of containment material in correspondence with said portion, and (b) insertion of at least one reference material in replacement of said volume of the block of containment material which has been removed.