Abstract
Cancer of unknown primary (CUP) with metastatic squamous cell carcinoma (SCC) to the neck nodes is rare and represents <5% of all head and neck malignancies. The prognosis is poor; hence, there is a need for early comprehensive diagnostic evaluation and management. A BRCA mutation is rarely seen in patients with head and neck squamous cell carcinoma (HNSCC) with an incidence of only 5-10%. We hereby present a rare case report of CUP with metastatic neck nodes (SCC), unveiling a BRCA mutation on liquid biopsy. The patient responded very well with platinum-based cytotoxic chemotherapy followed by maintenance poly adenosine diphosphate ribose polymerase inhibitors (PARPi). This is a first-of-its-kind case in the head and neck region, especially in this part of the world, where tobacco-related head and neck cancer catches all the attention over human papillomavirus (HPV) positivity and other risk factors.