No effective therapy exists for locally advanced or metastatic basal cell carcinoma (BCC). Vismodegib is a small molecule that is an inhibitor of the hedgehog pathway. An oral treatment to inactivate Smoothened would be a new therapeutic approach to treat advanced BCC. We studied two patients with advanced BCC and analysed variables, including age and sex of the patient, tumour location and size, time of evolution and nature of the tumour (primary or recurrent), type of treatment, route of administration, treatment duration, and treatment response. The most important side effects were determined. The patients received oral vismodegib (150 mg) daily. The male patient experienced difficulty in swallowing, which necessitated administration of the drug using a percutaneous endoscopic gastrostomy tube. In the first few months of treatment, both patients displayed significant improvement with almost complete disappearance of the skin lesions in one case and more than 50% in the other case. The median duration of response was 7.6 months. The side effects observed were of slight relevance; alopecia, dysgeusia, asthenia, and fatigue were easily resolved with the appropriate treatments. Vismodegib appears to be well tolerated and effective in treating advanced and metastatic BCC. No serious adverse events were reported.