Based on a Scandinavian research project, this article describes and discusses unusual/exceptional cases and how they may be approached methodologically. The aim of the presented project was to explore patient-defined unusual/exceptional positive courses of multiple sclerosis and cancer related to the use of complementary and alternative medicine. Such experience-based knowledge may be important both in a patient and public health perspective. I present different lay and professional definitions of unusual/exceptional courses and argue that a medical understanding should be combined with patients' perspectives. Central methodologists have argued that studies of unusual cases can illuminate both the unusual and typical aspects of a phenomenon, and that one may learn more by focusing in depth on understanding the needs, interests, and experiences of a small number of carefully selected study participants than by gathering standardized information from a large, statistically significant sample. I posit that qualitative and mixed research designs are suited in the study of unusual courses because they are individual and contain subjective and experience-based knowledge. In the presented research project, such in-depth knowledge contributed to several important hypotheses for further research.