Ipilimumab is a monoclonal cytotoxic T-lymphocyte-associated protein 4 antibody that has demonstrated improved survival in cutaneous melanoma. Little is known about the clinical impact of combining anti-cytotoxic T-lymphocyteassociated protein 4 therapy with radiation. Here we report a case of severe cutaneous desquamation in a 70-year-old female with vaginal/vulvar melanoma receiving concurrent ipilimumab and radiation therapy. The toxicity was successfully treated with oral/topical steroids and a break from treatment. This case underscores the importance of future research on optimal strategies for combining radiation with novel anti-tumour agents.