Background <p>Overdiagnosis is a major challenge in screening, leading to healthy individuals being diagnosed and treated for conditions that would never have caused harm. While evidence on overdiagnosis is growing, little is known about how health professionals (HPs) understand and engage with this phenomenon in practice. This study examines health professionals’ awareness, understanding and approaches to overdiagnosis in breast, lung, and prostate cancer screening.</p> Methods <p>This is a qualitative study with semi-structured interviews, using Positioning Theory as an analytical lens, among HPs involved in breast, prostate, or lung cancer screening in Flanders, Belgium, both in public health settings and in individual clinical care. 34 HPs, of whom 21 were purposively invited, because of their professional role, research background or public advocacy related to screening. In addition, 13 clinicians were randomly recruited from a list of registered physicians (GPs, gynaecologists, urologists and pneumologists).</p> Results <p>Few participants spontaneously mentioned overdiagnosis as a harm of screening, although most recognised it, primarily in relation to prostate cancer screening. Some HPs demonstrated a thorough understanding of overdiagnosis, but did not necessarily perceive it as a relevant harm. HPs’ perceptions and corresponding approaches depended primarily on their overall position regarding screening. The participating HPs articulated three different storylines to motivate their positions: (1) routine screening, where HPs accept screening as self-evident and are largely unaware of overdiagnosis, (2) determined screening, where HPs emphasise the evidence-based benefits of screening and acknowledge overdiagnosis, which they try to mitigate, but also de-problematise, and (3) cautious screening, where HPs question the evidence base and benefits of screening and consider overdiagnosis one of the reasons for adopting a reluctant position towards screening.</p> Conclusions <p>Participants rarely identify overdiagnosis as a harm of screening, despite being (passively) aware of it. HPs’ broader position on screening shapes how they understand, interpret, and respond to overdiagnosis and is primarily based on their knowledge of screening benefits, and influenced by professional contexts and personal characteristics. Regardless of their level of enthusiasm for screening, HPs with a more comprehensive understanding of its benefits and harms tend to adopt more deliberate and carefully considered - albeit divergent- approaches to overdiagnosis.</p> Clinical trial number <p>Not applicable.</p>