Patients with cystic fibrosis have increased risk for gastrointestinal cancer, lymphoid leukemia and testicular carcinomas. Chronic inflammation does not seem to be the only contributing factor. Mutations and epigenetic alterations in the CFTR gene may alter susceptibility to develop cancer. Lung cancer is up to now not frequently observed in CF patients. In lung cancer patients without CF low CFTR expression is significantly associated with advanced staging, lymph node metastasis. As the management and life expectancy of patients with cystic fibrosis have improved substantially in recent years, we expect an increased number of these patients diagnosed with lung cancer. In addition, it is possible that they, as a result of CFTR-dysfunction, will present with more aggressive lung tumors. Treating cancer in CF patients is a challenge because of multi-organ involvement and chronic colonization by resistant pathogens. The effectiveness and safety of immunotherapy in this population needs to be further evaluated.