Objectives: Among men with newly diagnosed prostate cancer, prostate-specific antigen (PSA) levels are higher and the cancer stage more advanced for African Americans than for whites. An earlier study found that after adjustment for literacy, race was no longer a significant predictor of advanced stage at presentation. We investigated whether, after adjusting for literacy, race was a significant independent predictor of greater PSA levels among men with newly diagnosed prostate cancer. Methods: Consecutive patients with newly diagnosed prostate cancer from four outpatient care facilities in Chicago were interviewed and given a literacy assessment (n = 308). The PSA level at diagnosis was obtained from the medical charts. Logistic regression models were used to identify predictors of high PSA levels (greater than 20 ng/mL) at presentation. Results: African-American men were three times more likely to have low literacy skills (sixth grade or less: 22.9% versus 7.1%; P <0.001) than were white men. In turn, men with low literacy skills were more than twice as likely to have a PSA level greater than 20 ng/mL at diagnosis (33.3% versus 13.5%; P = 0.009). On multivariate analyses, significant predictors of high PSA levels included low literacy (adjusted odds ratio 2.5, 95% confidence interval 1.5 to 4.2) and older age (age 65 to 74 years, adjusted odds ratio 2.6, 95% confidence interval 2.1 to 3.1 versus older than 74 years, adjusted odds ratio 3.4, 95% confidence interval 1.8 to 6.6), but not African-American race. Conclusions: In the current era in which PSA testing is common, low literacy may be an important and potentially overlooked factor associated with higher PSA levels at prostate cancer diagnosis among African-American and white men. © 2006 Elsevier Inc. All rights reserved.