The State of the Science Report by the National Cancer Institute on Symptom Management in Cancer identified gaps in understanding the epidemiology of pain, depression, and fatigue, and called for studies that will identify the extent of risk for these symptoms among those with cancer relative to other populations. Using year 2000 data from the Health and Retirement Study, a survey of a nationally representative sample of adults aged > or =50, we evaluated whether respondents with a history of cancer had excess risk for pain, depression, and fatigue compared to those without a history of cancer. We also compared clustering/co-occurrence of symptoms. Controlling for the confounding effects of comorbidities, sociodemographic, and access to care factors, respondents with a history of cancer had higher risk for fatigue (OR = 1.45; 95%CI = 1.29,1.63), depression (OR = 1.21; 95%CI = 1.06,1.37), and pain (OR = 1.15; 95%CI = 1.03,1.28). Symptom clusters were also more prevalent among those with a history of cancer (P < 0.001), with the pain-depression-fatigue cluster as most prevalent.