Combination targeted therapy with vemurafenib and cobimetinib has proved effective for metastatic melanoma. However, severe cutaneous adverse reactions have been reported, most frequently not only drug rash with eosinophilia and systemic syndrome but also rare Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) cases. We report a case of life-threatening episode of TEN following metastatic melanoma targeted therapy with vemurafenib and cobimetinib, with a long but successful patient recovery.