Objective: To investigate the value and applicability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) radiomics in differentiating primary lung cancer (PLC) from solitary lung metastasis (SLM) in patients with colorectal cancer (CRC). Materials and methods: This retrospective study included 103 patients with CRC and solitary pulmonary nodules (SPNs). The least absolute shrinkage and selection operator (LASSO) was used to screen for optimal radiomics features and establish a PET/CT radiomics model. PET/CT Visual and complex models (combining radiomics with PET/CT visual features) were developed. The area under the receiver operating characteristic (ROC) curve (AUC) was used to determine the predictive value and diagnostic efficiency of the models. Results: The AUC of the PET/CT radiomics model for differentiating PLC from SLM was 0.872 (95% CI: 0.806-0.939), which was not different from that of the visual (0.829 [95% CI: 0.749-0.908; p = .352]). However, the AUC of the complex model (0.936 [95% CI:0.892-0.981]) was significantly higher than that of the PET/CT radiomics (p = .005) and visual model (p = .001). The sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) of PET/CT radiomics for differentiating PLC from SLM were 0.720, 0.887, 0.806, 0.857, and 0.770, respectively. Conclusion: PET/CT radiomics can effectively distinguish PLC and SLM in patients with CRC and SPNs and guide the implementation of personalized treatment.