The familiarity difference cue has been regarded as a general cue for making inferential judgments (Honda, Abe, Matsuks, & Yamagishi in Memory and Cognition, 39(5), 851-863, 2011; Schwikert & Curran in Journal of Experimental Psychology: General, 143(6), 2341-2365, 2014). The current study tests a model of inference based on familiarity differences that encompasses the recognition heuristic (Goldstein & Gigerenzer, 1999, Goldstein & Gigerenzer in Psychological Review, 109(1), 75-90, 2002). In two studies, using a large pool of stimuli, participants rated their familiarity of cities and made choices on a typical city-size task. The data were fitted with the r-s model (Hilbig, Erdfelder, & Pohl in, Journal of Experimental Psychology: Learning Memory and Cognition, 37(4), 827-839, 2011), which was adapted to include familiarity differences. The results indicated that people used the familiarity difference cue because the participants ignored further knowledge in a substantial number of cases when the familiarity difference cue was available. An analysis of reaction-time data further indicated that the response times were shorter for heuristic judgments than for knowledge-only-based judgments. Furthermore, when knowledge was available, the response times were shorter when knowledge was congruent with a heuristic cue than when it was in conflict with it. Differences between the familiarity difference cue and the fluency heuristic (Schooler & Hertwig, 2005, Psychological Review, 112, 610-628) are discussed.