OBJECTIVES: The objective is to use a case study to explore if processes and outcomes of HTA evaluations for orphan drugs differ across different European countries, and, if so, how.   METHODS: England, France, Germany, Italy, Poland, Sweden and the Netherlands were selected as comparator countries to reflect their different HTA systems. A targeted literature search on specific HTA and related websites was carried out for each of the above countries. Pomalidomide was chosen for the exemplar because it has a clear single indication from the EMA. It was given orphan product designation in 2013 in combination with dexamethasone, for the treatment of relapsed and refractory multiple myeloma after previous therapies.  RESULTS: The results of this case study show that orphan drugs are not treated the same across the selected European countries, with varying recommendations. Two countries did not undertake an HTA assessment, Poland and the Netherlands. Of those that did conduct an assessment, England was the only country which did not recommended pomalidomide for its licensed indication. Italy recommended the use of pomalidomide, but requested additional safety monitoring of its use in clinical practice. In addition, there was more flexibility within the standard HTA process for orphan drugs within some countries. For example, “additional medical benefit” is assumed proven in Germany on the basis of the orphan designated marketing authorisation by the EMA, therefore IQWiG was not required to perform an HTA assessment.   CONCLUSIONS: This research is based on a case study of one product, so further research is still needed in this area. Despite this, it highlights the different approaches to the evaluation of orphan drugs across the selected countries. It will be important to explore what impact this has on patient access.