Background: Diagnostic assessment of chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME) is largely based on a two part process; screening patients who might meet criteria and following up this assessment with physicians’ clinical evaluation of a range of inclusionary symptoms and exclusionary illnesses. Purpose: The aim was to assess how well the DePaul Symptom Questionnaire (DSQ) screened for patients who were ultimately diagnosed by physicians using the Canadian Consensus Criteria (CCC). Methods: Sixty-four patients referred for evaluation of possible CFS or ME were screened initially using the DSQ, and then evaluated and subsequently diagnosed by physicians. To assess the consistency between the self-report DSQ and the physicians’ diagnosis, sensitivity and specificity as well as predictive values were calculated. Results: The DSQ identified 60 and the physicians identified 56 as having a CCC diagnosis. The overall agreement between the two ratings on the diagnostic assessment part was moderate (Kappa = 0.45, p < .001). The sensitivity of DSQ was good (98%) while the specificity was 38%. Positive and negative predictive values were 92% and 75%, respectively. Conclusion: DSQ is useful for detecting and screening symptoms consistent with a CCC diagnosis in clinical practice and research. However, it is important for initial screening of self-report symptoms to be followed up by subsequent medical and psychiatric examination in order to identify possible exclusionary medical and psychiatric disorders.