Color difference calculations are usually applied to match or tolerance of small differences between large (>2 degrees) visual fields. In contrast, we examine here the application of ultra-large color differences to enhance conspicuousness and discriminability of small (1 degrees subtense or smaller) visual targets, e.g., in visual information displays. We show that CIEDE2000, and color difference metrics based on the OSA Uniform Color Space and CIECAM02 are superior to CIELAB and CIELUV. Considering gray scale only, we show that Whittle's JND metric of achromatic contrast is as good as L* for this purpose, while also modeling contrast polarity and "crispening." Furthermore, using this JND metric, we replicate Highnote's finding that elongation of small targets affects their apparent contrast. We discuss the perceived fading of color differences when targets become smaller, and suggest practical methods to mitigate the adverse effect on color conspicuousness and discriminability. (C) 2009 Wiley Periodicals, Inc. Cot Res Appl, 35, 4-17, 2010; Published online 17 November 2009 in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/col.20557