This paper reports the process and experience of the design and conduct of a UK-based health technology assessment (HTA) of CYP2D6 pharmacogenetic testing to inform the targeted use of tamoxifen for the treatment of breast cancer. Examples of particular challenges for conducting a HTA are highlighted. It is clear from the HTA process described here that a common finding of similar future HTAs will have gaps in the evidence base, particularly in relation to evidence to inform cost–effectiveness. The lack of evidence is likely to be sufficiently large to result in extreme uncertainty and possibly decisions not to recommend a pharmacogenetic test for use in clinical practice. This has clear negative implications, which may hamper moving pharmacogenetic tests from the research environment into clinical practice and requires attention from both manufacturers of pharmacogenetic tests and key decision-makers responsible for market authorization and reimbursement.