This population-based study analyses familial risk as a factor in the development of head and neck squamous cell carcinoma before the age of 45. Two different designs were used: (1) estimation of standardised incidence ratios (SIRs) for cancer among first-degree relatives of 127 young head and neck cancer probands; and (2) estimation of odds ratios (ORs) for developing head and neck cancer associated with cancer in a first-degree relative. SIRs of cancer of the respiratory and upper digestive tract (lungs, oesophagus, and smoking-related head and neck sites [RUDT]) for first-degree relatives were 4.3 (95% confidence intervals or 95% CI of 1.6-9.5) for female patients, 1.0 (95% CI = 0.3-2.6) for male patients and 1.9 (95% CI = 0.9-3.5) for both sexes combined. ORs for head and neck cancer before the age of 45, in association with cancer of RUDT in a first-degree relative were 5.0 (95% CI = 1.4-17.3) for women, 1.1 (95% CI = 0.3-3.3) for men, and 2.0 (95% CI = 0.9-4.4) for both sexes combined. Hence, when analysing both sexes combined, our familial risk estimates for head and neck cancer showed non-significant increases. An explanation for the unexpected sex asymmetry in familial risk could be an interaction between inherent cancer susceptibility and a female biological characteristic. Alternatively, it could be artefacts caused by differences in familial smoking habits.