We present a case of a giant mature teratoma of the anterior mediastinum in a 35-year-old Caucasian woman. Following the onset of an episode of influenza associated with productive cough, the patient, an ex-smoker, underwent a chest X-ray which revealed the presence of a severe increase of the frontal cardiac area, with particular involvement of the atrial sectors and evident divarication of the sternal angle. Subsequent transthoracic echocardiography showed a rounded parenchyematous extra-cardial formation measuring approximately 9 cm in diameter and pressing against the lower posterior wall of the right atrium, with the chambers and valves of the heart being within the norm (Ejection Fraction = 71%), and an anomalous movement of the inter-ventricular septum. A thoracic computed tomographic scan with contrast medium confirmed the presence of a voluminous expansive formation with a maximum diameter of 125 mm, liquid contents, clear contours, multiple compartments, and parietal calcifications. This tumor was causing compression of the adjacent pulmonary parenchyma, the vascular and bronchial structures of the right lung (subsequently confirmed with fibrobronchoscopy), and the superior vena cava, without signs of infiltration. The tumor markers tested while the patient was hospitalized (α-fetoprotein, β-HCG, and CA 19-9) were within normal ranges. Her respiratory function tests showed a prevalent, obstructive type, slight ventilatory incapacity: forced expiratory volume in one second was 2.63 (73% of the former value), forced vital capacity was 3.63 (87% of the former value), and blood gases at baseline and after stress were within the normal range. The day after the patient was admitted to our hospital, she underwent surgery to excise the mediastinal mass with a median sternotomy approach. Once the mediastinal cavity was opened, it was possible to see the presence of the voluminous tumor, which occupied most of the right hemithorax with compression of the adjacent pulmonary parenchyma. There were also widespread adhesions to the superior vena cava, the ascending aorta, the pericardium, and part of the lower pulmonary lobe, where an atypical resection of pulmonary parenchyma was performed. The lesion measured 15 cm × 14 cm × 8 cm and showed smooth, regular external contours. The cut surface of the mass was cystic, filled with a yellowish white proteinaceous material admixed with hair. A thickened area of the cyst wall measuring 6.5 cm across was composed of a more solid white fibrous tissue, which also contained multiple small cysts filled with yellowish material. Fluid from the cysts in the mass was examined after removal, showing an amylase activity of 599 U/l despite serum levels being normal. Microscopically, the lesion resembled a mature cystic teratoma, which is more commonly seen in the ovary. The cystic wall was predominantly lined by a squamous epithelium associated with sebaceous glands, hair follicles, and a chronic inflammatory reaction. Other areas of the cyst showed a monostratified ciliated epithelium, cartilage, and mucinous glands recapitulating respiratory tract structures. More solid areas of the mass revealed pancreatic tissue with mature ductal and acinar structures intermixed with islets of Langerhans. In addition, in adipose tissue at the periphery of the mass, a thymic residue with prominent Hassall's corpuscles was identified. Careful examination of the mass did not reveal the presence of immature tissue. The post-operative period was uneventful, and the patient was discharged on post-operative day 10.