Disclosed are embodiments of a lithographic patterning method that incorporates a combination of photolithography and self-assembling copolymer lithography techniques in order to create, on a substrate, a grid-pattern mask having multiple cells, each with at least one sub-50 nm dimension. The combination of different lithographic techniques further allows for precise registration and overlay of the individual grid-pattern cells with corresponding structures within the substrate. The resulting grid-pattern mask can then be used, in conjunction with directional etch and other processes, to extend the cell patterns into the substrate and, thereby form openings, with at least one sub-50 nm dimension, landing on corresponding in-substrate structures. Once the openings are formed, additional structures can be formed within the openings.