Immune checkpoint inhibitors (ICI) have become an essential part of cancer treatment. Anti-programmed cell death receptor-1 (PD-1) is a monoclonal antibody that targets PD-1. For patients with inoperable cutaneous squamous cell carcinoma, anti-PD-1 ICI treatment has been approved as monotherapy or in adjunct with other treatment modalities. A patient primarily treated with PD-1 inhibition for local advanced moderately differentiated cutaneous squamous cell carcinoma involving the parotid and the neck is presented. Surgical therapy would be extensive including pinnectomy, radical parotidectomy, neck dissection, resection of the temporal and mastoid bones, and free flap reconstruction. Anti-PD-1 ICI was started as a first-line treatment and a complete clinical response was observed after 5 cycles of treatment. The patient is disease-free within the follow-up period of 17 months. Although a complete response to anti-PD-1 receptor antibodies was observed, off-target toxicities are a risk and not all patients will benefit from a response.