The present study develops an improved technique for evaluating the effectiveness of different methods of application of a commercially available biocide containing a quaternary ammonium formulation to reduce biocolonization on building stone. In anticipation of cleaning biocolonization from the Smithsonian’s National Museum of the American Indian, the biocide was test applied to surplus blocks of dolomitic limestone left from the building’s construction. The new technique avoids subjective visual judgments by comparing areas based on digital photography using a special set up, with data processed using commercially available software. Statistical analysis quantifies differences between application methods.