OBJECTIVES: Basal cell carcinoma (BCC), the most common non-melanoma skin cancer in the UK, is effectively treated with surgery and/or radiotherapy. However, BCC can become locally advanced (laBCC) and potentially no longer amenable to surgery or radiotherapy (NATSOR). Limited data exist on the burden of illness associated with laBCC. The primary aim of this study was to estimate the cost burden of laBCC(NATSOR) in the UK. METHODS: Demographics, medical history, prescriptions, and cost data for patients with BCC with linked records were extracted from primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care databases. As no separate diagnosis code exists for laBCC, a patient identification algorithm was developed in collaboration with UK experts. Patients first treated for laBCC between January 2007-December 2012 with ≥2 years follow-up were indexed. Non-laBCC controls were propensity-matched on year of birth and BCC diagnosis, sex, and comorbidities. Pairs where controls had BCC-related events ≤2 years before case indexing were excluded. RESULTS: Of 103,852 patients extracted, 64,126 were included in the algorithm, of whom 159 had laBCC (NATSOR). In 29 control-matched cases (after applying exclusion criteria), patients with laBCC utilised more healthcare resources (range, £301.11-5,742.77) than controls (range, £18.27-4,491.36), with a significant difference in overall annualized burden/patient of £1,241.58 (P=.0002). A sensitivity analysis (omitting the BCC-related event criterion) in 52 matched pairs yielded an annualized burden/patient of £1,193.95 (P<.0001). Main drivers of cost in both analyses were minor skin and ear procedures (specialized surgeries to prevent loss of function for lesions in/around the ear can be expensive and technically challenging). CONCLUSIONS: These analyses indicate that laBCC (NATSOR) imposes a greater per-patient burden on the UK healthcare system than non-laBCC. Our estimated burden of laBCC (NATSOR) is likely conservative due to methodology and database limitations, such as lack of cancer drug and complete radiotherapy data in the database.