The present invention provides apparatus and methods for performing endoscopic mucosal resection and endoscopic submucosal dissection of tissue. In a first embodiment, a catheter having proximal and distal ends and a balloon disposed near the distal end of the catheter is provided. A portion of the distal end of the catheter is configured to be inserted beneath a section of mucosal tissue having a lesion, and the balloon is configured to be inflated to lift the mucosal tissue in an upward direction, thereby facilitating removal of the tissue comprising the lesion. Optionally, a surgeon may advance a needle knife through the catheter to further incise submucosal tissue while the balloon is in the inflated state. If desired, a flushing fluid may be provided to a target site during the procedure.