The increasing number of new cases of cancer highlights the relevance of primary prevention for cancer control, which is influenced, among other factors, by the population’s health-related knowledge. Therefore, we aimed to describe cancer-related knowledge in Portugal, including perception of risk, awareness of cancer causes and preventive behaviours. We evaluated 1624 Portuguese-speaking dwellers, aged between 16 and 79 years, through face-to-face interviews conducted using a structured questionnaire. We computed adjusted (sex, age, education) regression coefficients and prevalence ratios, using linear and Poisson regression, respectively, to quantify associations with cancer-specific knowledge. The proportions of nonresponse ranged from 13.4 to 63.5% for the most frequent cancer in Portugal and the leading cause of cancer, respectively. The mean of the estimated lifetime risk of cancer in the Portuguese population was 37.0%. A total of 47.5% of the respondents identified breast cancer as the most frequent in Portugal, 72.0% named lifestyles as the leading cause of cancer and 40.2% selected not smoking as the most important preventive behaviour. Lower levels of education were associated with higher proportions of nonresponse, but not consistently with inaccurate knowledge. Men provided lower estimates of the lifetime risk of cancer, indicated breast cancer less frequently and more often lung cancer as the most frequent, and were more likely to select not smoking as the most important preventive behaviour. The present study provides relevant data on knowledge of cancer prevention, which may be used for the planning and evaluation of awareness-raising and primary prevention interventions in Portugal.