Background. Recent studies have found that knowledge about cancer prevention and treatment differs across ethnic and socioeconomic status (SES) backgrounds, which could directly impact our decisions to engage in protective health behaviors. In this study, we examined sociodemographic-based differences in cancer knowledge and health beliefs and examined differences in the accuracy of the cancer knowledge based on health beliefs. Methods. Cross-sectional surveys were conducted between July 1995 and March 2004 on adult, healthy, cancer-free control participants (N=2074; 50% male) enrolled into a molecular epidemiological case-control study. Most were non-Hispanic white, 14% were African American, and 8% were Hispanic. Participants were personally interviewed on 6 items assessing health beliefs and 10 items assessing cancer knowledge. Results. Unadjusted differences in cancer knowledge were observed by gender, age, ethnicity, household income, educational attainment, and smoking status. After adjusting for the other sociodemographic characteristics, women had more accurate knowledge than men, the accuracy of knowledge increased with higher educational attainment and annual household income, and never smokers had more accurate knowledge than ever smokers (P<.01 for all). Moreover, accurate cancer knowledge was associated with protective health beliefs; eg, the belief that changing health habits was worthwhile was associated with more accurate knowledge. Conclusions. Results emphasize the need to develop health education programs that enhance cancer knowledge among individuals of low SES and foster protective health beliefs.