OBJECTIVES: Overall 2506 patients gained access (from a total of 2880 applications) for oncology treatment from the Cancer Drugs Fund within the first 6 months of its launch. However, there are significant variations in the number of applications that different Strategic Health Authorities (SHAs) are able to process and approve. This study aims to assess the underlying reasons for the observed inter regional variability in the application rates, processing and outcomes within the Cancer Drugs Fund from October 2010 to March 2011. METHODS: The results on the application rates from an audit undertaken by Rarer Cancers Foundation using the Freedom of Information Act were analysed, especially, the change in application rate over time and the outcomes of these requests. The analysis led to the development of a framework to understand the key factors influencing the application rates and its outcomes, which was then validated through a telephone survey of key SHAs in 2011. RESULTS: Along with significant variations in the application rate, there appears to be a north-south divide, with SHAs in the south of England approving a lower proportion of applications. Some of the underlying reasons were identified to be linked with administration costs, levels of routine access to cancer treatments (which itself vary according to the area of the country) and ‘timely’ decision-making ability. CONCLUSIONS: Some of the notable practices identified towards expediting the processing of applications can form recommendations for robust process development in future for the upcoming clinical commissioning consortia to guide their commissioning activities. Future steps can include benchmarking of their application approval rates by clinical commissioning consortia (and SHAs until 2013) against that in other region and take action to identify the outliers and address the causes of this.