Roughly 1.1 million cases of cutaneous squamous cell carcinoma (cSCC) occur annually. Although most cases can be cured with local therapy, up to 8,000 deaths from metastatic cSCC (mcSCC) occur each year, a number similar to that of melanoma. 1 With no US Food and Drug Administration–approved options available for mcSCC, common approaches include platinum-based chemotherapy and off-label cetuximab. These strategies lack durability, and overall survival for mcSCC is only 10.9 months. 2 Clinical responses in mcSCC have recently been reported with the use of PD-1 antibodies, pembrolizumab and nivolumab. 3, 4, 5 Here we report a complete pathologic response after 4 cycles of nivolumab and the anti–CTLA-4 antibody, ipilimumab, in a patient with mcSCC.