A method for fabricating a back-side illuminated image sensor includes providing a semiconductor substrate having a front surface and back surface, providing a plurality of transistors, metal interconnects, and metal pads on front surface of the substrate, bonding a supporting layer to the front surface of the substrate, thinning-down the semiconductor substrate from the back surface, clearing-out a region of the semiconductor substrate from the back surface that covers a fine alignment mark by performing registration from the back surface and using a global alignment mark as a reference, and processing the back surface of the substrate by performing registration from the back surface and using the fine alignment mark as a reference.