To develop and validate predictive models using clinical parameters, radiomic features and a combination of both for preoperative differentiation of pulmonary nodular mucinous adenocarcinoma (PNMA) from pulmonary tuberculoma (PTB).A total of 124 and 53 patients with PNMA and PTB, respectively, were retrospectively analyzed from January 2017 to November 2022 in The Fourth Affiliated Hospital of Hebei Medical University (Ligang et al., A machine learning model based on CT and clinical features to distinguish pulmonary nodular mucinous adenocarcinoma from tuberculoma, 2023). A total of 1037 radiomic features were extracted from contrast-enhanced computed tomography (CT). The patients were randomly divided into a training group and a test group at a ratio of 7:3. The least absolute shrinkage and selection operator (LASSO) algorithm was used for radiomic feature selection. Three radiomics prediction models were applied: logistic regression (LR), support vector machine (SVM) and random forest (RF). The best performing model was adopted, and the radiomics score (Radscore) was then computed. The clinical model was developed using logistic regression. Finally, a combined model was established based on clinical factors and radiomics features. We externally validated the three models in a group of 68 patients (46 and 22 patients with PNMA and PTB, respectively) from Xing Tai People's Hospital (30 and 14 patients with PNMA and PTB, respectively) and The First Hospital of Xing Tai (16 and 8 patients with PNMA and PTB, respectively). The area under the receiver operating characteristic (ROC) curve (AUC) value and decision curve analysis were used to evaluate the predictive value of the developed models.The combined model established by the logistic regression method had the best performance. The ROC-AUC (also a decision curve analysis) of the combined model was 0.940, 0.990 and 0.960 in the training group, test group and external validation group, respectively, and the combined model showed good predictive performance for the differentiation of PNMA from PTB. The Brier scores of the combined model were 0.132 and 0.068 in the training group and test group, respectively.The combined model incorporating radiomics features and clinical parameters may have potential value for the preoperative differentiation of PNMA from PTB.© 2023. The Author(s).