This study investigates whether listeners' familiarity with an intonation contour affects speech processing. In three experiments, Dutch participants heard Dutch sentences with normal intonation contours and with unfamiliar ones and performed word-monitoring, lexical decision, or semantic categorisation tasks (the latter two with cross-modal identity priming). The unfamiliar intonation contour slowed down participants on all tasks, which demonstrates that an unfamiliar intonation contour has a robust detrimental effect on speech processing. Since cross-modal identity priming with a lexical decision task taps into lexical access, this effect obtained in this task suggests that an unfamiliar intonation contour hinders lexical access. Furthermore, results from the semantic categorisation task show that the effect of an uncommon intonation contour is long-lasting and hinders subsequent processing. Hence, intonation not only contributes to utterance meaning (emotion, sentence type, and focus), but also affects crucial aspects of the speech comprehension process and is more important than previously thought.