Rejection, either acute or chronic, represents the main cause of organ dysfunction in patients with cystic fibrosis (CF) undergoing lung transplantation and its development negatively impacts on long term survival in these patients. The aim of this retrospective study is the identification of early biomarkers for molecular diagnosis of acute cellular rejection (ACR), antibody-mediated rejection (AMR) and chronic lung allograft dysfunction (CLAD), based on the computational analysis of clinical, laboratory and omics data. 48 CF patients who underwent lung transplant at Padua Center from 2005 to 2016 were recorded, and their clinical, pathological and laboratory data were collected at each scheduled follow-up time, to identify any type of rejection. Peripheral blood mononuclear cells (PBMCs), bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) have already organized according to a well-defined protocol adopted for transcriptomics. The possibility of crucial biomarkers wold led to improve early diagnosis of rejection and to a better care for patients with CF undergoing lung transplantation.