Abstract Background Leather dust is an established carcinogen of the sinonasal cavities; however, evidence is lacking regarding its association with other head and neck cancers (HNC). To date, few studies have been conducted on the association between occupational leather dust exposure and the risk of oral, pharyngeal, and laryngeal cancers. The objective of this study was to investigate the association between the risk of HNC and occupational exposure to leather dust. Methods Lifestyle habits and occupational history were collected for 2161 patients with squamous cell carcinoma of oral cavity, pharynx, and larynx, and 3555 controls, using a standardized questionnaire. Occupational exposure to leather dust was assessed using a job-exposure matrix. Odds ratios (OR) and 95% confidence intervals (CI) for HNC globally and by subsite were estimated using multivariate unconditional, and polytomous logistic regressions, respectively. Results Cumulative lifetime exposure to leather dust