8522 Background: A cancer symptom cluster of pain, depression and fatigue has been proposed. We evaluated the frequency and strength of association between these symptoms in advanced cancer, and the risk factors for experiencing all three. Methods: Symptoms from 1,000 patients presenting to a palliative medicine program were recorded prospectively. Possible clustering of pain, depression and fatigue was tested (Spearman correlations). Univariate and multivariate logistic regression analyses were performed of demographics, disease site, laboratory and clinical risk factors for the presence all three symptoms. Results: No association was found between pain and depression (r=0.051, p=0.13), or pain and fatigue (r=0.001, p=0.97) and little between depression and fatigue (r=0.173, p<0.001). 27% (n=261) had all three symptoms and in 9% (n=71) all were moderate or severe. Univariate predictors for the presence of all three were: anorexia-cachexia, anxiety, dyspnea, nausea, sleep problems (all p<0.001), vomiting (p=0.007), and younger age (p=0.007). Univariate predictors of moderate-severe pain, depression and fatigue were: anorexia and early satiety (p<0.001), anxiety (p<0.001), dyspnea (p=0.004), low creatinine (p=0.07), poor performance status (p=0.002), sleep problems (p=0.002), >10% weight loss (p=0.046) and vomiting (p=0.047). Those with pain, depression and fatigue had a median 12 (range 2–24) other symptoms vs. 5 (range 1–14) if none were present (p<0.001). Multivariate predictors of pain, depression and fatigue were: anxiety OR 3.81 (95% CI 2.74–5.30, p<0.001); early satiety OR 1.86 (1.35–2.56, p<0.001); nausea OR 1.44 (1.05–1.97, p=0.023); sleep problems OR 1.52 (1.11–2.08, p=0.009); weight loss OR 1.47 (1.08–2.01, p=0.016). Multivariate predictors of moderate-severe pain, depression and fatigue were anorexia OR 3.11 (1.74–5.55, p<0.001); anxiety OR 6.53 (3.64–11.73, p<0.001); poor performance status OR 1.49 (1.09–2.04, p=0.012). Conclusions: The 3 symptoms co-occur in 1 in 4 advanced cancer patients. Risk factors include younger age, symptom burden and the anorexia-cachexia syndrome. Pain, depression and fatigue do not cluster in advanced cancer. No significant financial relationships to disclose.