Objective: To analyze the role of transoral robotic base-of-tongue mucosectomy in a cohort of patients with human papilloma virus negative unknown primary carcinoma. Study Design: Retrospective database analysis. Methods: A retrospective database review from 2012 to 2018 was performed at two large tertiary centers to study patients with human papilloma virus (HPV)-negative unknown primary carcinoma who underwent transoral robotic base-of-tongue mucosectomy. P16 testing was used as a surrogate for HPV status. Patients were included that had squamous cell carcinoma metastatic to the lateral neck based on fine needle aspiration or open biopsy. Preoperatively, all patients were classified as having an unknown primary based on normal clinical and flexible endoscopic exam, normal operative endoscopy, nonlocalizing imaging, and tonsillectomy. All patients underwent robotic base-of-tongue mucosectomy. The primary outcome measure was the incidence of pathologic identification of a mucosal primary. Results: Twenty-three patients with p16-negative unknown primary carcinoma were identified and studied. All patients underwent transoral robotic base-of-tongue mucosectomy. Median age was 60 years at the time of diagnosis, and 18 of 23 (78.2%) were male. Pathologic analysis of the base-of-tongue specimens showed a primary tumor in only three of 23 (13.0%) of patients. Conclusion: Despite prior evidence suggesting a high rate of primary site identification in HPV-related disease, robotic base-of-tongue mucosectomy may not be indicated for HPV-negative unknown primary carcinoma based on a low likelihood of finding the primary. Level of Evidence: 4 Laryngoscope, 131:78–81, 2021.