Although XPC’s essential role in the recognition of bulky DNA lesions and subsequent activation of GG-NER, when altered, is a leading mechanism for development of UV-induced dermatologic malignancies and in modifications of cancer response to chemotherapies including cisplatin, recent data support a non-canonical role of XPC in DNA damage response and repair mechanisms, tumor suppressor transcriptional regulation, and in the development of non-dermatologic malignancies. Here, XPC is linked to cancer.