Background: The Delirium Observation Screening Scale (DOS) was developed to facilitate early recognition of delirium by nurses during routine clinical care. It has shown good validity in a variety of patient populations, but has not yet been validated in hospitalized patients with advanced cancer, although the DOS is commonly used in this setting in daily practice. The aim of this study was to evaluate the accuracy of the DOS in hospitalized patients with advanced cancer using the revised version of the Delirium Rating Scale (DRS-R- 98) as the gold standard. Methods: Patients with advanced cancer admitted to the medical oncology ward were screened for delirium with the DOS and DRS-R-98. Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of the DOS were calculated, using a DOS score ≥ 3 as a cut-off for delirium. Results: Ninety-five DOS negative and 98 DOS positive patients were identified. Sensitivity of the DOS, was > 99.9% (95%-CI, 95.8-100.0%), specificity was 99.5% (95%-CI 95.5-99.96%), PPV was 94.6% (95% CI 88.0-97.7), and NPV was > 99.9% (95% CI 96.1-100.0). Conclusions: The DOS is an accurate screening tool for delirium in patients with advanced cancer. Since it has the benefit of being easily implicated in daily practice, we recommend to educate caregivers to screen patients with advanced cancer by DOS analysis. By early recognition and adequate treatment of this distressing delirium syndrome the quality of life of patients with advanced cancer can be improved. Trial registration: ClinicalTrials.gov Identifier NCT01539733 (Feb 27, 2012 - retrospectively registered), Netherlands Trial Register NTR2559 (Oct 7, 2010).