Objectives: (a) To determine the prevalence of unexplained symptoms among newly referred patients in a Dutch academic outpatient clinic for general neurology; (b) To identify factors that can serve as characteristics and possibly as screening instruments for unexplained symptoms in this population. Methods: Observational study, consisting of self-assessment questionnaires. Patients and resident neurologists completed self-designed questionnaires, which included questions about possible features of unexplained symptoms. Patients also completed the Hospital Anxiety and Depression Scale (HADS), evaluating the existence of anxiety and depressive symptoms. Diagnosis of unexplained symptoms was based on the final classification of the patient's symptoms as non-organic, after assessment by a senior neurologist. In the analysis, separate predicting factors and groups of factors were adjusted for age, sex and HADS-score, and analysed as possible characteristics of unexplained symptoms. Results: 35% of the patients (208 total, 174 completed questionnaires) were considered to suffer from unexplained symptoms. Young age (p < 0.001) and female sex (p = 0.007) were significantly associated with unexplained symptoms, high HADS-scores were not (p = 0.10). Characteristics associated with unexplained symptoms were the resident's preliminary impression of symptoms being non-organic, after reading of the referral letter [OR 96.8, 95% confidence interval (95%-CI) 29.7-315, PPV 82%, NPV 96%] and after the first encounter (OR 305, 95%-CI 37.3-2494.6, PPV 83%, NPV 98%), but before the actual history taking and neurological examination. The only other non-demographic characteristic of unexplained symptoms was a visit in order to obtain a second opinion (OR 2.43, 95%-CI 1.15-5.10). Clustering of these factors, however, did not have sufficient predictive power to result in an accurate screening instrument. Conclusions: Unexplained symptoms are common in the neurology outpatient clinic and are to some extent predicted by the physician's preliminary judgement of symptoms. However, history taking and neurological examination remain indispensable for the detection of less obvious organic disorders.