OBJECTIVE: The aim was to study symptoms managed as the main problem by the general practitioner (GP) and to describe the frequencies and characteristics of presented symptoms when no specific diagnosis could be made. DESIGN: Cross- sectional study. SETTING: General practices in the Central Denmark Region. SUBJECTS: In total, 397 GPs included patients with face-to-face contacts during one randomly assigned day in 2008-2009; 7008 patients were included and 5232 presented with a health problem. MAIN OUTCOME MEASURES: GPs answered a questionnaire after each patient contact. Symptoms and specific diagnoses were subsequently classified using the International Classification of Primary Care (ICPC). Symptom frequency, comorbidity, consultation length, and GP-assessed final outcome and burden of consultations were analysed. RESULTS: The GPs could not establish a specific diagnosis in 36% of patients with health problems. GPs expected that presented symptoms would not result in a future specific diagnosis for half of these patients. Musculoskeletal (lower limb and back) and respiratory (cough) symptoms were most frequent. More GPs had demanding consultations when no specific diagnosis could be made. Higher burden was associated with age, comorbidity, and GP expectancy of persistent symptoms when no diagnosis could be made. CONCLUSION: Interpretation and management of symptoms is a key task in primary care. As symptoms are highly frequent in general practice, symptoms without a specific diagnosis constitute a challenge to GPs. Nevertheless, symptoms have been given little priority in research. More attention should be directed to evidence-based management of symptoms as a generic phenomenon to ensure improved outcomes in the future.