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Depression is a common health problem among patients with cancer. The Edmonton Symptom Assessment System (ESAS) is one of many tools that have been used to evaluate depression in these patients. Nevertheless, the diagnostic performance and the appropriate cutoff point of the ESAS for the assessment of depression in these patients have varied in the studies.To determine the diagnostic accuracy and the optimal cutoff point for the ESAS for the assessment of depression in patients with cancer.PubMed, Scopus, CINAHL, and Cochrane library databases from inception to September 18, 2016.Paired reviewers independently screened abstracts and full-text articles for all cross-sectional studies published in English and compared these with the ESAS in the depression (ESAS-D) subscale with reference to standard tests for the assessment of depression.Two reviewers serially abstracted the data and independently assessed the risk of bias by using the Quality Assessment of Diagnostic Accuracy Studies 2.A total of 6 studies were eligible for review. Our meta-analysis showed the optimal cutoff point of the ESAS-D ≥ 4, with pooled sensitivity and specificity at 53% (95% confidence interval [CI]: 38%-67%) and 90% (95% CI: 82%-94%), respectively. The positive likelihood ratio and diagnostic odds ratio of the ESAS-D ≥ 4 were 5.2 (95% CI: 3.1-8.6) and 10 (95% CI: 5-19). There was a high degree of heterogeneity between the studies (P value <.001, I2 = 96%).We suggest that an ESAS-D ≥ 4 could be used to detect possible cases of depression in patients with cancer.Our study protocol was registered with the International Prospective Register of Systematic Reviews on October 4, 2016, and was last updated on January 11, 2017 (registration number CRD42016048288).