Objective: Thrombocytosis is commonly observed in patients with solid tumors. This study aimed to evaluate the prognostic role of circulating pretreatment platelet count in a large series of patients with head and neck squamous cell carcinoma (HNSCC). Methods: We retrospectively studied 824 patients with HNSCC treated at a single institution from 2000 to 2012. Disease-specific survival and local, regional, and distant recurrence-free survival were analyzed according to the distribution of the platelet count. Results: By defining the platelet count 250.05 x 10(9)/L as a cut-off point with the best predictive capacity, we classified the patients into two groups: those with a high platelet count (n = 378, 45.9%), and those with a low platelet count (n = 446, 54.1%). On univariate analysis, there were significant differences in disease-specific survival depending on pretreatment platelet count (P = 0.001). The 5-year specific survival rates were 74.1% (CI 95%: 69.8-78.4%) and 61.6% (CI 95%: 56.4-66.8%) for patients with a low and high platelet count, respectively. According to the results of a multivariate analysis, patients with a high count of platelets had a tendency to a lower disease-specific survival, but the hazard ratio did not reach statistically significant differences (HR 1.24, CI 95%: 0.97-1.61, P = 0.085). Conclusion: Platelet count was significantly associated with survival in univariate analysis. However, in a multivariate analysis it lost its prognostic capacity, limiting its utility as a prognostic marker in patients with HNSCC. Considering separately each primary tumor location, patients with hypopharyngeal cancer and a high platelet count had a significant decrease of disease-specific survival. (C) 2016 Elsevier Ireland Ltd. All rights reserved.