A biopsy system comprises a control module, a localization assembly, a biopsy device, and a targeting cube. The biopsy device comprises a holster portion and a probe. The probe and/or other associated components are configured to selectively couple with a targeting cube that is configured to selectively couple with a grid plate having apertures for receiving the targeting cube. The targeting cube comprises a body defined by faces. The targeting cube further comprises guide holes that originate and terminate at the faces and pass through the body of the targeting cube to provide a passageway through the targeting cube. The body of the targeting cube is at least partially comprised of elastomeric material to allow for compression of the body. The elastomeric material may thus provide a secure fit with a wide range of grid plates having openings of various shapes and sizes.