Basal cell carcinoma (BCC) is the most common human malignancy of skin and Australia has the highest incidence of BCC in the world. The number of advanced BCC (aBCC) cases in Australia is increasing. However, new personalised medicines are now available to treat aBCC and are highly effective. Laboratory diagnosis of aBCC can be challenging using routine histology. Molecular genetic tests for routine use in the diagnostic lab are not yet available. Innovative immunohistochemistry panels can help correctly identify this group of patients and thereby allow them access to effective personalised medicine. In this article, we review the epidemiology, genetics and treatment of aBCC with particular focus on the role of immunohistochemistry in laboratory diagnosis of this increasingly common cancer.