The aim of this study was to clarify the clinicopathological characteristics and the prognostic factors of combined pulmonary fibrosis and emphysema (CPFE), which is defined as pulmonary emphysema associated with idiopathic pulmonary fibrosis (IPF). Of 92 IPF patients admitted to our hospital during the past 6 years, 35 were diagnosed as CPFE (Group E) and 57 as IPF without emphysema (Group F). We retrospectively compared the clinical features between these 2 groups. Furthermore, we investigated the histopathological localization and characteristic background parenchymal architecture of lung cancer in 6 patients with CPFE who had undergone surgical lung resection for complications of lung cancer. Lastly, we compared the histopathological differences in background lung structures of the origins of the lung cancers in the following 3 groups: Group E, Group F, and pulmonary emphysema. The smoking index values and the incidence of lung cancer were higher in patients in Group E than in Group F, but the survival times were significantly lower in Group E patients. The prognostic factors included emphysema, lung cancer, pulmonary arterial hypertension, increased composite physiological index, and acute exacerbation. Histopathologically, the localization of lung cancer in Group E patients was adjacent to emphysematous lesions with or without associated fibrosis, which showed a more marked architectural distortion with less significant fibroblastic foci, collapse of alveoli, and subpleural fibrosis than in Group F patients. In conclusion, this study demonstrated that the incidence of lung cancer was extremely high in patients with CPFE. However, the prognosis was unfavorable regardless of the presence of lung cancer, with the chief adverse prognostic factor being complications of pulmonary emphysema. Emphysematous lesions with fibrosis in Group E that are different from those seen in Group F may be background lung structures characteristic of the carcinogenesis of lung cancer.