A biopsy system comprises a control module, a localization assembly, a biopsy device, and a targeting cube. The biopsy device comprises a probe and other components, which 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, and guide holes that originate and terminate at the faces and pass through the body of the targeting cube to provide passageways through the targeting cube. The body of the targeting cube is at least partially comprised of elastomeric material to allow for adjustment of the orientation of the passageways. The body of the targeting cube is further comprised of malleable members that flank the passageways and allow for angulation of an instrument, such as by maintaining an adjusted orientation of a passageway into which the instrument is inserted.