Objective: To explore worry and decision-making processes used by faecal immunochemical test (FIT)-positive participants in the Dutch national screening programme for colorectal cancer. Methods: A mixed-methods study consisting of 22 semi-structured interviews in FIT-positive participants who underwent the recommended colonoscopy within 4–6 months after the FIT result, followed by a widespread questionnaire in a larger target population (N = 1495). Results: In the interviews, we recognised two different decision-making processes. The first is an affective heuristic decision process where the decision to participate is made instantly and is paired with high-risk perception, worry and (severe) emotional turmoil. The second is a more time-consuming analytical decision process in which participants describe discussing options with others. In the questionnaire, high levels of cancer worry (CWS > 9) were reported by 34% of respondents. Decisional difficulties were reported by 15% of respondents, and 34% of respondents reported discussing the positive FIT result with their GP. Individuals with high levels of cancer worry contacted their GP less often than those with low levels. Conclusions: The Dutch two-step screening programme may result in high levels of cancer worry in a non-cancer population. More research is needed to monitor worry and its role in decision-making in cancer screening, as well as ways to facilitate decision-making for participants.