Explicit similarity judgments tend to emphasize relational information more than do difference judgments. We propose and test the hypothesis that this asymmetry arises because human reasoners represent the relation different as the negation of the relation same, so that processing difference is more cognitively demanding than processing similarity. For both verbal comparisons between word pairs, and visual comparisons between sets of geometric shapes, we asked participants to select which of two options was either more similar to or more different from a standard. On unambiguous trials, one option was unambiguously more similar to the standard; on ambiguous trials, one option was more featurally similar to the standard, whereas the other was more relationally similar. Given the higher cognitive complexity of assessing relational similarity, we predicted that detecting relational difference would be particularly demanding. We found that participants (1) had more difficulty accurately detecting relational difference than they did relational similarity on unambiguous trials, and (2) tended to emphasize relational information more when judging similarity than when judging difference on ambiguous trials. The latter finding was captured by a computational model of comparison that weights relational information more heavily for similarity than for difference judgments. Our results provide convergent evidence for a representational asymmetry between the relations same and different.