Methods of measuring variation across multiple instances of a pattern on a substrate or substrates after a step in a device manufacturing process are disclosed. In one arrangement, data representing a set of images is received. Each image represents a different instance of the pattern. The set of images are registered relative to each other to superimpose the instances of the pattern. Variation in the pattern is measured using the registered set of images. The pattern comprises a plurality of pattern elements and the registration comprises applying different weightings to two or more of the plurality of pattern elements. The weightings control the extent to which each pattern element contributes to the registration of the set of images. Each weighting is based on an expected variation of the pattern element to which the weighting is applied.