Semi-structured, in-depth interviews have long been recognized as the gold standard method of data collection, most notably in those qualitative research studies that aim to investigate illness-related experiences. This particular interview style can be free flowing when required, allowing deep exploration of the respondent’s comments to gain greater understanding of matters of particular interest. The ability to probe specific issues provides a way of assessing the perspectives of the respondent/interviewee, their individual understanding, values, beliefs, experiences, and perceptions, and allowing those nuanced accounts to become the primary source of knowledge to explore in greater depth and breadth. Nevertheless, conducting a semi-structured in-depth interview can be difficult to do well. It requires the researcher/interviewer to maintain focus on both the objectives of the interview, and the features of interviewee’s previous comments, at the same time. To be successful in this, the researcher/interviewer needs to be able to be both flexible and responsive to deal with factors which emerge that might be unanticipated. This case study describes three scenarios in which the unanticipated happened during an interview with a patient, and the response taken by the researcher. Following each scenario, the researcher reflected on what happened at the time; why it might have happened as it did; the impact it had on both her, the patient, and the research; and she poses how a similar situation, should it occur again in the future, may be handled differently.