Background: Mediastinal affections are common and encompass a great number of different diagnoses. Objective: To analyze the clinical aspects and the therapeutic response of 114 patients with mediastinal diseases treated at the Thoracic Surgery Department of Santa Casa de Sao Paulo Hospital, from 1979 and 1997. Method: The patients were grouped according to the benign or malignant nature of the disease, and the two groups were compared regarding gender, age bracket, symptomatology, topography of the lesion, mortality, and response to treatment. Results: Sixty-three patients had neoplasia: 31 benign and 32 malignant. Fifty-one cases were not neoplastic. No difference was found between the groups regarding gender or age bracket. Half of the patients were between 20 and 49 years of age. The anterior mediastinum was the most frequently affected compartment (66 patients), followed by the upper mediastinum (18 patients), the posterior mediastinum (16 patients), and the middle mediastinum (14 patients). The most frequent histological types were: benign thymus diseases (N = 40), mesenchymal tumors (N = 17), lymphomas (N = 15), neural tumors (N = 9), and germ cell tumors (N = 8). Malignant tumors were more frequently symptomatic (91%), and benign tumors were more frequent in asymptomatic patients (92%). The most frequent symptoms were related to myastenia gravis, followed by dyspnea and chest pain. Weight loss, anorexia and fever were significantly more frequent in patients with malignant neoplasias. Conclusions: Regarding the clinical aspects we can state that benign lesions were predominant, that mediastinal diseases were more prevalent in young adults, and that benign lesions were more frequent in asymptomatic patients. Treatment (clinical/surgical) was effective in most patients, benefiting approximately 90% of the patients with benign affections and 45% of the patients with malignant tumors. In 73% of the benign affections, surgical treatment was capable of achieving the cure. Mortality resulting from complications was 1.75%.