OBJECTIVES: This paper examines how different payers and health technology assessment (HTA) agencies recognise and reward innovation, using treatments for breast and colorectal cancer as case studies. METHODS: Breast and colorectal cancer were chosen given the extent of clinical advancements to date and supporting publicly-available data. Sixteen cancer medicines across these two tumour types were considered. For each medicine/indication, the reimbursement decision and the reasons behind it were obtained from assessment reports published by the respective agencies in Australia, Canada, England and Wales, France and Scotland. RESULTS: Seventy-seven decisions were reviewed (39 and 38 for breast and colorectal cancer respectively). Twenty-four (62%) and 16 (42%) were positive for breast and colorectal cancer respectively, while 21% and 45% were negative. In general, HTA agencies appear to consider advancements in breast cancer treatments as representing good uses of health care resources with some assessments yielding less positive or more restrictive results. The majority of appraisals for newer colorectal cancer treatments have failed to receive positive recommendations. CONCLUSIONS: We identified some broad areas where differences of approach have led to different decisions. These relate to the: 1) acceptability of surrogate endpoints (e.g. progression-free survival) in cases where improvement in overall survival has not been established; 2i) extent to which agencies formally consider input from clinical and patient representative organisations as part of their decision-making process; 3) methods used to assess medicines where pivotal trial did not use a comparator reflecting standard therapy; and 4) mechanisms for re-review or adopting performance-based risk-sharing arrangements following rejection due to uncertain clinical and/or cost effectiveness. Addressing these issues may improve the likelihood of innovative medicines meeting reimbursement requirements, for breast and colorectal cancer as well as other therapeutic areas, thereby increasing the overall health benefit from pharmaceutical development that accrue to patients.