BACKGROUND: Medically unexplained dyspnea (MUD) refers to a condition characterized by a sensation of dyspnea and is typically applied to patients presenting with anxiety and hyperventilation without cardiopulmonary explanations for their dyspnea. The diagnosis is difficult. We investigated whether descriptors of dyspnea and associated symptoms of MUD are differentially diagnostic. METHODS: A respiratory symptom checklist incorporating 61 spontaneously reported descriptors of dyspnea was administered to 96 patients with MUD and 195 patients with cardiopulmonary diseases. Symptom factors measuring different qualitative aspects of dyspnea were derived by a principal component analysis. The separation of two patient groups in terms of symptom factors was achieved by a discriminant analysis. RESULTS: Five factors grouped different attributes of dyspnea: urge to breathe, depth and frequency of breathing, difficulty breathing and phase of respiration, wheezing, and affective dyspnea. The other five factors grouped symptoms of anxiety, tingling, cough and sputum, palpitation, and out of control. A discriminant analysis allowed to separate two patient groups (R(2) = 0.45, p < 0.0001). The presence of urge to breathe, affective dyspnea, anxiety, and tingling pointed to the diagnosis of MUD, whereas the reporting of wheezing, cough and sputum, and palpitation indicated cardiopulmonary diseases. The sensitivity was 85%, and specificity was 88%. CONCLUSIONS: Descriptors of dyspnea and associated symptoms allows satisfactory separation of patients with MUD from patients with cardiopulmonary diseases. A prospective study will be required to test the validity and predictive values of the descriptor model in another cohort of patients.