Systems and methods for the orientation of soft tissue such as breast tissue for enhanced accuracy of imaging and/or procedures such as a biopsy or excision are disclosed. The system for orientating and maintaining the orientation of soft tissue generally includes a frame defining an opening, the frame being configured to orient and immobilize an area of soft tissue positioned on one side of the opening, an attachment mechanism to secure the frame to an attachment region defined by the area of soft tissue or by a skin surface overlying the area of soft tissue, to facilitate orienting and immobilizing the area of soft tissue, and an imaging device to image the area of soft tissue. The opening may allow a probe of the imaging device or imaging energy transmitted by the imaging device to be movable therein for image scanning of the soft tissue. The probe, e.g., an ultrasound transducer can be rotated within the frame such that the probe scans at least either of two perpendicular directions within the frame. The frame may be adjustable in at least one dimension in order to adjust the size of the frame opening so as to facilitate the scanning and positioning of the probe within the frame opening. The frame may be attached and secured to the soft tissue with vacuum, adhesive, and/or clips or hooks. The soft tissue may be stretched into a desire orientation prior to attachment of the frame. An anchored lift member may be connected to the frame so as to slightly lift the frame and thus position and immobilize the soft tissue to which the frame is attached. Lifting of the soft tissue improves and enhances a tissue separation process using a tissue separation device. A connector may connect the imaging device to the tissue separation device to maintain a portion of the tissue separation device within the image plane of the probe to further improve and enhance the tissue separation process.