Background In South Africa, the rate of histologically diagnosed prostate cancer is 40.1 per 100 000 in whites and 14 per 100 000 in blacks. However, blacks have limited access to diagnostic facilities and present late with an advanced disease. Knowledge about prostate cancer in the South African male population is necessary in order to increase the acceptance of early prostate cancer screening. Objective This study assessed the knowledge of prostate cancer among men attending the urology outpatient clinic at a tertiary hospital in South Africa. Methods A cross-sectional study was conducted from February to March 2010. A structured questionnaire was administered to participants using consecutive sampling of eligible patients and consisted of sections on sociodemographic details and knowledge about prostate cancer. A total of 346 males, 35 years of age and older, participated in the study. Results The majority of the respondents (n = 258; 75.0%) were black, married (n = 220; 64.0%), from the Free State Province (n = 320; 92.8%), and had access to television (n = 248; 71.7%). Only 38 (11.0%) knew the three main symptoms and signs associated with prostate cancer. Level of school education, race and language were statistically significantly associated with level of knowledge whereas age and marital status were not. Conclusion More than half (54.4%) of the respondents had not heard of prostate cancer. The majority of men who had heard of prostate cancer had a moderate level of knowledge. The factors significantly associated with level of knowledge need to be considered in educational campaigns, prostate cancer screening and treatment.