Detectable wear based on traditional gravimetric, dimensional, and profilometric approaches consumes the original wear surface along with any evidence of the incipient wear and running-in processes. Measurement sensitivity to asperity-scale wear is needed for more fundamental studies of the macroscale wear process. One promising solution is the topographical difference method in which a worn surface is subtracted from a reference surface. In theory, topographical differences circumvent the sensitivity limitations of traditional approaches. In practice, uncertainty in the topography measurements and repositioning errors limit its potential. In this study, we assessed the sensitivity limitations of the topographical difference method in terms of absolute worn volume and locational tracking of asperity-scale wear using typical surfaces, topography measurements, and surface repositioning. The results demonstrate that the method can precisely track the gradual wear of a single asperity in a macroscopic tribological contact and quantify it with the help of a post-hoc image repositioning technique even via relatively imprecise repositioning of the scanning surface.