OBJECTIVES: A growing body of evidence links effective physician-patient communication to desirable outcomes such as improved adherence to treatment and higher satisfaction of both patient and physician. However, when it comes to rare diseases, the patient is forced to become knowledgeable about his own disease state and therapies. Our objective was to describe and specify the experiences of patient-physician-interaction in rare diseases, to develop an empirically derived typology of interaction patterns and to explore the challenges associated with each of these patterns. METHODS: We designed a multi-case study as a series of semi standardized interviews with patients suffering from rare diseases. Therefore we extracted six different rare diseases: Amyotrophic lateral sclerosis, Marfan’s syndrome, Wilson’s disease, Epidermolysis bullosa, Duchenne muscular dystrophy and Neurodegeneration with brain iron accumulation. A total of 120 interviews were recorded, transcribed and analyzed thematically based on emerging codes.   RESULTS: As suggested, insufficient expertise of the health care providers proved to be a major problem in the highly specialized treatment process of rare diseases. Here, it is often the patient himself who becomes an expert to determine what kind and how much service he needs. Thus, we could identify the patient-directed interaction as a widely experienced communication pattern among patients with rare diseases. Physician´s ability and willingness to accept the patient as an expert emerged as a major determinant for patient satisfaction. CONCLUSIONS: People with rare diseases often face challenges due to the low prevalence and the resulting lack of knowledge among their providers. Our study showed the relevance of the provider´s ability to acknowledge the active role of the patient as an informed, involved and interactive partner in the treatment process. However, allowing the patient to control therapy may require a change of mind-set with some long-standing traditional roles in healthcare.