The main purpose of this study was to develop and validate a clinical model for estimating the risk of malignancy in solitary pulmonary nodules (SPNs).A total of 672 patients with SPNs were retrospectively reviewed. The least absolute shrinkage and selection operator algorithm was applied for variable selection. A regression model was then constructed with the identified predictors. The discrimination, calibration, and clinical validity of the model were evaluated by the area under the receiver-operating-characteristic curve (AUC), calibration curve, and decision curve analysis (DCA).Ten predictors, including gender, age, nodule type, diameter, lobulation sign, calcification, vascular convergence sign, mediastinal lymphadenectasis, the natural logarithm of carcinoembryonic antigen, and combination of cytokeratin 19 fragment 21-1, were incorporated into the model. The prediction model demonstrated valuable prediction performance with an AUC of 0.836 (95% CI: 0.777-0.896), outperforming the Mayo (0.747, p = 0.024) and PKUPH (0.749, p = 0.018) models. The model was well-calibrated according to the calibration curves. The DCA indicated the nomogram was clinically useful over a wide range of threshold probabilities.This study proposed a clinical model for estimating the risk of malignancy in SPNs, which may assist clinicians in identifying the pulmonary nodules that require invasive procedures and avoid the occurrence of overtreatment.