OBJECTIVES: Sunitinib is an oral multitargeted tyrosine kinase inhibitor approved in Europe in 2010 for use in well-differentiated pancreatic neuroendocrine tumors (pNET) that have spread or cannot be removed with surgery. This study evaluated the cost-effectiveness of sunitinib + best supportive/palliative care (BSC) compared to placebo + BSC in Portuguese patients. METHODS: A Markov model was adapted to predict life-years (LY) and associated costs (€) of pNET patients’ treatment over lifetime in Portugal. The model tracks transitions of patients between three health states: progression free, post-progression and death. Transition probabilities between health states and adverse events probabilities were based on published results from the phase III pNET trial of sunitinib. BSC overall survival (OS) probabilities were adjusted for crossover with a rank preserving structural failure time (RPSFT) statistical analysis. Resource use was elicited through a panel of five Portuguese experts with extensive clinical experience. Subsequent treatments are not included given the lack of efficacy evidence. Adverse events treatment costs and unit costs were extracted from Portuguese literature and official sources. A National Health Service perspective was adopted and both costs and effectiveness were discounted at 5%. RESULTS: Average cost per patient for sunitinib + BSC and placebo + BSC treatment were 54,215€ and 10,239€ respectively, while the average effectiveness gained with sunitinib was 1.83LY. This resulted in an incremental cost-effectiveness ratio (ICER) of 24,035€/LY. While the application of the RPSFT method may have some limitations and therefore provide uncertainty regarding the true OS benefit, the intent-to-treat classic analysis that does not correct for the confounding effect of crossover generated an ICER of 34,387€/LY. CONCLUSIONS: Compared with BSC, sunitinib treatment in patients with advanced or metastatic unresectable pNET improve effectiveness in terms of life-years gained and is cost-effective by the commonly used threshold in Portugal for assessment of new health technologies.