Using a multidimensional assessment of health literacy (the Cancer Message Literacy Test-Listening, the Cancer Message Literacy Test-Reading, and the Lipkus Numeracy Scale), the authors assessed a stratified random sample of 1013 insured adults (40-70 years of age). The authors explored whether low health literacy across all 3 domains (n =111) was associated with sets of variables likely to affect engagement in cancer prevention and screening activities: (a) attitudes and behaviors relating to health care encounters and providers, (b) attitudes toward cancer and health, (c) knowledge of cancer screening tests, and (d) attitudes toward health related media and actual media use. Adults with low health literacy were more likely to report avoiding doctor's visits, to have more fatalistic attitudes toward cancer, to be less accurate in identifying the purpose of cancer screening tests, and more likely to avoid information about diseases they did not have. Compared with other participants, those with lower health literacy were more likely to say that they would seek information about cancer prevention or screening from a health care professional and less likely to turn to the Internet first for such information. Those with lower health literacy reported reading on fewer days and using the computer on fewer days than did other participants. The authors assessed the association of low health literacy with colorectal cancer screening in an age-appropriate subgroup for which colorectal cancer screening is recommended. In these insured subjects receiving care in integrated health care delivery systems, those with low health literacy were less likely to be up to date on screening for colorectal cancer, but the difference was not statistically significant.