OBJECTIVES: Capacity constraints jeopardize health care systems’ sustainability all over the world while the number of Health Technology Assessment (HTA) agencies continues to increase. Explicit or implicit use of cost-effectiveness thresholds based on HTA/economic evaluations should indicate whether a technology is worth its costs. Personalized cancer medicine (PCM) promises to be different from established technologies raising the question whether decision making also differs for PCM. Our goal was to identify cost-effectiveness thresholds in general or specific to PCM to finally provide input for decision makers and expert panels. METHODS: A conceptual evaluation framework was developed comprising eight domains including 93 items. We enhanced our previous selection of only European HTA agencies (IQWiG, DAHTA@DIMDI, NICE, HAS, SBU) by AHRQ, MSAC, LBI, BIQG / GOEG, CADTH, DECIT-CGATS, HITAP. Information was collected and compared quantitatively, choosing the item ‘cost-effectiveness threshold’ as key information. Additionally, HTA agencies’ methodological guidelines were extracted for PCM relevant information. Finally, information was entered into the database and compared qualitatively. RESULTS: First five agencies differed highly in eight domains (organization scope, processes, methods, dissemination, decision, implementation, and impact). They agreed in only 17-40%. Enhancement by further agencies indicates continued heterogeneity. UK (US$32.000-48,000) and Thailand (US$9,866) indicated explicit but generic (i.e. not specific to disease or type of technologies) thresholds; implicit use was identified in five countries (Australia, Brazil, Canada, Sweden, USA). Germany explicitly uses disease-specific cost-effectiveness ratios. In none of the included countries cost-effectiveness thresholds specific to personalized medicine and/or oncology were identified, even though we found exception rules in UK. CONCLUSIONS: Based on a systematic and comprehensive contextual framework displaying HTA in 10 countries of four continents we identified large heterogeneity in the application of HTA. Specific guidance for innovative and costly cancer interventions is lacking.