HIV-infected patients frequently present with advanced stage cancer. It is possible that late stage presentation may be related to lack of cancer knowledge and/or barriers to care. Questionnaires were administered to 285 adult HIV-infected patients to evaluate knowledge of cancer risk factors and symptoms and barriers to care between 2011 and 2012. Differences in mean and percent scores by group were assessed using a t test for independent samples and chi-square analysis, respectively. Respondents were predominantly male (64%), African-American (86%), and low income (60% < $10,000/year). Thirty-four (12%) had been diagnosed with cancer, and 169 (59%) had a family history of cancer. The mean knowledge score was 17.5 out of 24 questions (73%). Mean scores were not significantly different by sex, age, race, or income. Respondents with a college education scored significantly higher than those with less than a high school education (p < 0.01). In unadjusted analysis, a higher proportion of patients with a personal/family history of cancer (74%) scored in the highest quartile (>70% correct) compared to those without any personal history of cancer (62%) (p = 0.03). There was a higher level of cancer knowledge in this population compared to studies that have evaluated the HIV-uninfected population. Nevertheless, there were knowledge deficits, suggesting the need for further education about cancer to improve earlier detection rates and, ultimately, outcomes.