OBJECTIVES: A common application of personalized medicine is testing for thiopurine S-methyltransferase (TPMT) status prior to treatment with thiopurine drugs which are used to treat several auto-immune disorders and acute lymphoblastic leukemia (ALL). The objective was to systematically review guidelines that include statements regarding TPMT testing to 1) investigate variations in testing and dosing recommendations and 2) appraise their quality.  METHODS: Citation databases, websites and online repositories were searched. Guidance documents were compared within therapeutic areas. A quality appraisal was carried out by three appraisers using AGREE-II. Scores were recorded for domains related to Scope and purpose, Stakeholder involvement, Rigor of development, Clarity of presentation, Applicability and Editorial independence. Guidance documents were scored and ranked according to quality. RESULTS: A total of 20 guidelines were reviewed, covering inflammatory bowel disease (IBD) (n=8), inflammatory skin disorders (n=3), autoimmune hepatitis (n=3), rheumatic disease (n=2), ALL (n=2) and pharmacogenetics in general (n=2).  Six documents focused on paediatric patients.  Five specifically recommended genotyping while four recommended phenotyping.  The remainder included general statements. Thirteen documents included dosing recommendations based on TPMT status, with the most common recommendation to avoid treatment in patients with extremely low or absent TPMT activity and to reduce thiopurine doses in patients with intermediate TPMT activity.  Five documents recommended adjustments of a typical dose for each TPMT genotype or phenotype.  Wide variation in quality was observed across all domains.  Guidance documents that included dosing recommendations demonstrated higher quality. CONCLUSIONS: Variations in TPMT testing recommendations reflect the need for clarity in the clinical validity and utility of alternative TMPT test methods.  The variable quality among guidelines illustrated a lack of consistency and rigor in the methods used to develop recommendations. Interdisciplinary collaboration between experts in genetics, pharmacology and clinical disciplines and careful adherence to methods for evidence-based guideline development is warranted.