Novelty indicators are increasingly important for science policy. This paper challenges the indicators of novelty as an atypical combination of knowledge (Uzzi et al., 2013) and as the first appearance of a knowledge combination (Wang et al., 2017). We exploit a sample of 230,854 articles (1985 - 2005), published on 8 journals of the American Physical Society (APS) and 2.4 million citations to test the indicators using (i) a Configuration Null Model, (ii) an external validation set of articles related to Nobel Prize winning researches and APS Milestones, (iii) a set of established interdisciplinarity indicators, and (iv) the relationship with the articles’ impact. We find that novelty as the first appearance of a knowledge combination captures the key structural properties of the citation network and finds it difficult to tell novel and non-novel articles apart, while novelty as an atypical combination of knowledge overlaps with interdisciplinarity. We suggest that the policy evidence derived from these measures should be reassessed.