OBJECTIVES: Palbociclib, a novel therapeutic option for metastatic breast cancer (MBC), was approved as therapy for patients with HR-positive, HER2-negative MBC that has progressed on prior endocrine therapy, in combination with fulvestrant, by FDA. This study evaluated the cost-effectiveness of adding palbociclib as a second-line endocrine therapy of MBC from the perspective of US payers and identified the range of drug costs for which the addition of palbociclib could be considered cost-effective in the context of Chinese heath care. METHODS: A Markov model was constructed to estimate lifetime costs and quality-adjusted life-years (QALYs) to predict the cost-effectiveness of palbociclib in Asian and non-Asian patients. One-way and probabilistic sensitivity analyses were performed to predict the uncertainty varied by parameter inputs in the model. RESULTS: In the United State, palbociclib provided an additional 0.23 QALYs at a cost of $112,068/QALY in the United States. The palbociclib arm added costs of $46,087 resulting in ICERs of $526,433 per QALY gained. In China, when palbociclib cost $0.073 and $0.2867/mg, the ICERs approximated the WTP thresholds of $23,484 and $51,422/QALY, respectively. CONCLUSIONS: For the United States, adding palbociclib is unlikely to be cost-effective compared with fulvestrant treatment for MBC that has progressed on prior endocrine therapy at the current price. For China, the economic outcomes of palbociclib must be further characterized.