BACKGROUND: Diagnostic uncertainty is common, but its communication to patients is under-explored. This study aimed to (1) characterise variation in doctors' communication of diagnostic uncertainty and (2) explore why variation occurred. METHODS: Four written vignettes of clinical scenarios involving diagnostic uncertainty were developed. Doctors were recruited from five hospitals until theoretical saturation was reached (n = 36). Participants read vignettes in a randomised order, and were asked to discuss the diagnosis/plan with an online interviewer, as they would with a 'typical patient'. Semi-structured interviews explored reasons for communication choices. Interview transcripts were coded; quantitative and qualitative (thematic) analyses were undertaken. RESULTS: There was marked variation in doctors' communication: in their discussion about differential diagnoses, their reference to the level of uncertainty in diagnoses/investigations and their acknowledgement of diagnostic uncertainty when safety-netting. Implicit expressions of uncertainty were more common than explicit. Participants expressed both different communication goals (including reducing patient anxiety, building trust, empowering patients and protecting against diagnostic errors) and different perspectives on how to achieve these goals. Training in diagnostic uncertainty communication is rare, but many felt it would be useful. CONCLUSIONS: Significant variation in diagnostic uncertainty communication exists, even in a controlled setting. Differing communication goals-often grounded in conflicting ethical principles, for example, respect for autonomy versus nonmaleficence-and differing ideas on how to prioritise and achieve them may underlie this. The variation in communication behaviours observed has important implications for patient safety and health inequalities. Patient-focused research is required to guide practice. PATIENT OR PUBLIC CONTRIBUTION: In the design stage of the study, two patient and public involvement groups (consisting of members of the public of a range of ages and backgrounds) were consulted to gain an understanding of patient perspectives on the concept of communicating diagnostic uncertainty. Their feedback informed the formulations of the research questions and the choice of vignettes used.