Minimally invasive video-assisted thoracoscopic surgery (VATS) is considered as an alternative to thoracotomy for early stage lung cancer. Since 2009, we use a VATS approach for all early stage lung tumors as well as benign indications for lung lobectomy. As experience with the technique is growing, indications are expanded. Here, we report our first minimally invasive pneumonectomies of two patients with non-small cell lung cancer (NSCLC). Case 1: A 60-year-old man was diagnosed with a centrally located tumor of the right lung invading all three lobes without any obvious lymph node metastasis in the preoperative work-up. The patient was scheduled for a right-sided VATS pneumonectomy. Case 2: A 62-year-old woman was diagnosed with a centrally located tumor of the left lung with an ipsilateral positron emission tomography (PET) positive lymph node (aortopulmonary window). After neoadjuvant treatment, the patient was scheduled for a left-sided pneumonectomy. Written informed consent was given in both cases. The procedures were completed using three incisions. A complete mediastinal lymph node dissection was performed. The postoperative courses were uneventful. VATS pneumonectomy is feasible in highly selected cases. It offers all advantages known from minimally invasive lung lobectomy with less pain and faster rehabilitation, which might facilitate the delivery of adjuvant treatment.