A multi-patterning method of manufacturing a patterned wafer provides test structures designed to enhance overlay error measurement sensitivity for monitoring and process control. One or more patterns are overlaid on a first pattern, each of a given pitch, with the elements interleaved. Test structure is formed with elements of the overlaid patterns spaced away from respective mid-positions more closely toward elements of the first pattern. In some embodiments, test structure elements of the second pattern are overlaid midway between mid-positions of elements of the first pattern and measured by scatterometry. In other embodiments, test structure elements of the second pattern are overlaid at a slightly different pitch than the elements of the first pattern and measured by reflectivity. Measurements are compared with library measurements to identify the error, which may be fed back to control the patterning process. The multi-patterning may be formed by LELE, LLE, LFLE, or other methods.