Methods are provided for generating nucleic acid fingerprints from complex nucleic acid populations. The methods rely on the addition of a nucleic acid tag with at least two functional domains to members of the complex population being assessed. Primers specific to the appended tag and arbitrary or adapter-specific primers are used to amplify subsets of the complex population. The amplified population is then used to generate labeled products for comparative expression analysis using the functional domain of the appended tag sequence that was not used for amplification. The separation of amplification and labeling substantially reduces the number of false positives common in amplification fingerprinting experiments by removing all amplification products from the analysis that do not derive from the anchored ends of the nucleic acid population.