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Abstract Various processes, including benign or malignant (mostly metastasis) processes, contribute to the occurrence of multiple pulmonary nodules. For differential diagnosis, metastasis must be excluded as an etiological factor in patients who have multiple pulmonary nodules with a known primary malignancy. However, differential diagnosis of multiple pulmonary nodules caused by benign diseases and malignant processes is challenging. Multiple pulmonary nodules resulting from metastasis may mimic those resulting from infections, inflammatory processes, and rare benign diseases. Some rare diseases, such as pulmonary sclerosing pneumocytoma and pulmonary epithelioid hemangioendothelioma, or common diseases with a rare presentation of multiple nodules must be considered in the differential diagnosis of metastasis. In addition to the clinical and laboratory findings, radiological features are crucial for differential diagnosis. The size, density, location, and border characteristics (well-defined or poorly defined) of pulmonary nodules, as well as their internal structure (solid, subsolid, or ground glass nodule), growth rate during follow-up, and associated pulmonary and extrapulmonary findings are important for differential diagnosis along with clinical and laboratory data. This article summarizes the general features and imaging findings of these diseases, which less frequently present with multiple pulmonary nodules, and the clues that can be used to distinguish these diseases from metastasis. Critical relevance statement The radiological features, clinical findings, and temporal changes during follow-up are important in distinguishing non-metastatic causes of multiple pulmonary nodules from metastatic causes and guiding diagnosis and early treatment, especially in patients with primary malignancy. Key Points Multiple pulmonary nodules have a wide range of etiologies, including metastatic disease. Metastasis as an etiology must be excluded in patients with multiple pulmonary nodules. Correlation of radiological findings (nodule size, position, and associated findings) with clinical history is crucial for differential diagnosis. Graphical Abstract