Low body mass index (BMI) has been associated with risk of head-neck cancer (HNC), but prospective data are scarce. We investigated the association between BMI, BMI at age 20 years and change in BMI during adulthood with risk of HNC and HNC subtypes. 120,852 participants completed a questionnaire on diet and other cancer risk factors, including anthropometric measurements, at baseline in 1986. After 20.3 years of follow-up, 411 HNC (127 oral cavity cancer (OCC), 84 oro-/hypopharyngeal cancer (OHPC), and 197 laryngeal cancer (LC)) cases and 3,980 subcohort members were available for case-cohort analysis using Cox proportional hazards models. BMI at baseline was inversely associated with risk of HNC overall, with a multivariate rate ratio of 3.31 (95% CI 1.40-7.82) for subjects with a BMI <18.5 kg/m(2), compared to participants with a BMI of 18.5 to 25 kg/m(2). Among HNC subtypes, this association was strongest for OCC and OHPC. The association between BMI at age 20 and HNC risk appeared to be positive. In this large prospective cohort study, we found an inverse association between BMI at baseline and HNC risk. For BMI at age 20, however, a positive rather than inverse association was found.