AbstractBackgroundTumor deposits (TDs) are an infrequently mentioned feature of head and neck squamous cell carcinoma (HNSCC) that are currently grouped under extranodal extension (ENE) in the AJCC 8th edition of HNSCC TNM staging. The prognostic implication of TDs in comparison to ENE remains uncertain.MethodsThis observational, retrospective, non‐randomized study evaluated patients with HNSCC who underwent initial surgical resection, with neck dissection and adjuvant radiotherapy ± chemotherapy. Clinical variables were considered, and statistical analyses were conducted to compare time progression and overall survival (OS) in patients with TDs against those with ENE.ResultsOf the 71 patients included in the study, 50 were diagnosed with ENE (pN2a‐ENE in 38 patients and pN3b‐ENE in 12), while 21 had TDs ± ENE. The median time to progression was significantly different based on the presence of ENE or TDs (p = .002) and pN2a‐ENE/pN3b‐ENE or TDs (p = .007). The three‐year OS was 55.7% for the entire group, 60.4% in ENE and 38.4% in TDs (p = .021). The OS difference between the pN2a‐ENE, pN3b‐ENE, and the TDs group was also significant (p = .05). The hazard ratio between ENE and TDs was Exp (B) 4.341 (p = .044).ConclusionsTDs in HNSCC are associated with a lower OS than ENE, despite intensified adjuvant therapy. Our results confirm a better prognosis for pN2a‐ENE vs. pN3b‐ENE, and pN3b‐ENE vs. TDs. TDs may serve as an indicator of poor prognosis and require separate TNM classification in HNSCC staging. Larger studies are needed to evaluate TDs impact on treatment strategies and outcomes.