To develop and validate a CT-based radiomic model to simultaneously diagnose anaplastic lymphoma kinase (ALK) rearrangements and epidermal growth factor receptor (EGFR) mutation status of lung adenocarcinoma and to assess whether peritumoural radiomic features add value in the prediction of mutation status.503 patients with pathologically proven lung adenocarcinoma containing information on the mutation status were retrospectively included. Intratumoural and peritumoural radiomic features of the primary lesion were extracted from CT. We proposed two-level stepwise binary radiomics-based classification models to diagnose ALK (step1) and EGFR mutation status (step2). The performance of proposed models and added value of peritumoural radiomic features were evaluated by using the areas under receiver operating characteristic curves (AUC) and Obuchowski index in the development and validation sets.Regarding the prediction of ALK rearrangement, the diagnostic performance of the intratumoural radiomic model showed the AUC of 0.77 and 0.68 for the development and validation sets, respectively. As for EGFR mutation, the diagnostic performance of the intratumoural radiomic model showed the AUCs of 0.64 and 0.62 for the development and validation sets, respectively. The radiomics added value to the model based on clinical features (development set [radiomics + clinical model vs. clinical model]: Obuchowski index, 0.76 vs. 0.66, p < 0.001; validation set: 0.69 vs. 0.61, p = 0.075). Adding peritumoural features resulted in no improvement in terms of model performance.The CT radiomics-based model allowed the simultaneous prediction of the presence of ALK and EGFR mutations while adding value to the clinical features.