Highly multiplexed genomics assays are challenged by the need for a sufficient signal-to-noise ratio for each marker scored on a microarray-detection platform. Typically, as the number of markers scored (or target complexity) increases, either more assay-target material must be applied to the array or the specific activity of each marker must be proportionately increased. However, hybridization of excessive amounts of target to the microarray can result in elevated nonspecific binding and consequent degradation of information. We have found that quantum dots provide a successful alternative to organic dyes for achieving highly multiplexed (>20,000-plex) and highly accurate, four-color genotyping and have the additional advantage of being excitable by a single wavelength of light despite their distinct emission wavelengths.