To develop a radiomics nomogram based on computed tomography (CT) images that can help differentiate lung adenocarcinomas and granulomatous lesions appearing as sub-centimeter solid nodules (SCSNs). The records of 214 consecutive patients with SCSNs that were surgically resected and histologically confirmed as lung adenocarcinomas (n = 112) and granulomatous lesions (n = 102) from 2 medical institutions between October 2011 and June 2019 were retrospectively analyzed. Patients from center 1

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... enrolled as training cohort (n = 150) and patients from center 2 were included as external validation cohort (n = 64), respectively. Radiomics features were extracted from non-contrast chest CT images preoperatively. The least absolute shrinkage and selection operator (LASSO) regression model was used for radiomics feature extraction and radiomics signature construction. Clinical characteristics, subjective CT findings, and radiomics signature were used to develop a predictive radiomics nomogram. The performance was examined by assessment of the area under the receiver operating characteristic curve (AUC). Lung adenocarcinoma was significantly associated with an irregular margin and lobulated shape in the training set (p = 0.001, < 0.001) and external validation set (p = 0.016, = 0.018), respectively. The radiomics signature consisting of 22 features was significantly associated with lung adenocarcinomas of SCSNs (p < 0.001). The radiomics nomogram incorporated the radiomics signature, gender and lobulated shape. The AUCs of combined model in the training and external validation dataset were 0.885 (95% confidence interval [CI]: 0.823-0.931), 0.808 (95% CI: 0.690-0.896), respectively. Decision curve analysis (DCA) demonstrated that the radiomics nomogram was clinically useful. A radiomics signature based on non-enhanced CT has the potential to differentiate between lung adenocarcinomas and granulomatous lesions. The radiomics nomogram incorporating the radiomics signature and subjective findings may facilitate the individualized, preoperative treatment in patients with SCSNs.