The invention is directed to devices and methods for accessing a desired target site within a patient's body and for separating and collecting a tissue specimen from the target site. The device includes a probe member or cannula with a penetrating distal tip, and a tissue cutting member which is disposed within the probe member to cut a tissue specimen from supporting tissue at the biopsy site. This probe is releasably secured to a housing to provide a plurality of discrete orientations of the probe about its longitudinal axis. Vacuum may be provided to the inner lumen of the cutting member to transport tissue through the inner lumen thereof. Rotation (and optionally longitudinal reciprocation) of the tissue cutter is effective to separate a tissue specimen from surrounding tissue at the target site. Vacuum or fluid pressure may be used to move the specimen cut from the target site proximally within the inner lumen defined at least in part by the culling member for collection.