This report describes a case involving the diagnosis and treatment of squamous cell carcinoma (SCC) of the duodenum, which was found to be a metastatic lesion originating from recurrent head and neck cancer (HNC) in a 74-year-old female patient. The patient had a past medical history of gastroesophageal reflux disease (GERD), tonsillar SCC, and recurrent HNC. She presented with symptoms of burning, tingling, and numbness of the throat and left side of the tongue. Upon examination with an esophagogastroduodenoscopy, an ulcerated hard area mass was detected in the third portion of the duodenum. Biopsy results confirmed the mass to be a metastatic poorly differentiated SCC.The incidence of head and neck squamous cell carcinoma (HNSCC) metastasis to the duodenum is rare, likely due to the unique anatomic location and the lack of lymphatic drainage in the area. The patient was treated with a combination of paclitaxel, carboplatin, and pembrolizumab. This case underscores the significance of considering unusual sites of metastasis in HNSCC patients and utilizing advanced imaging modalities and immunotherapy to detect and treat these locations effectively.