Not every round spot on a radiological image is a solitary pulmonary nodule: it may be confused with the projection of a structure of the chest wall or skin, such as a nipple, a healing rib fracture or electrocardiographic monitoring.

The most important cause to exclude is any form of lung cancer,[5] including rare forms such as primary pulmonary lymphoma, carcinoid tumor and a solitary metastasis to the lung (common unrecognised primary tumor sites are melanomas, sarcomas or testicular cancer).

The most common benign coin lesion is a granuloma (inflammatory nodule), for example due to tuberculosis or a fungal infection, such as Coccidioidomycosis.

Lung nodules can also occur in immune disorders, such as rheumatoid arthritis or granulomatosis with polyangiitis, or organizing pneumonia.

[9] CT densitometry, measuring absolute attenuation on the Hounsfield scale, has low sensitivity and specificity and is not routinely employed, apart from helping to distinguish solid from ground glass lesions, and to confirm visible fatty areas or calcifications.

[8] More frequent CT scans than what is recommended has not been shown to improve outcomes but will increase radiation exposure and the unnecessary health care can be expected to make the patient anxious and uncertain.

[6] In selected cases, nodules can also be sampled through the airways using bronchoscopy or through the chest wall using fine-needle aspiration (which can be done under CT guidance).

[21] Where workup indicates a high risk of cancer, excision can be performed by thoracotomy or video-assisted thoracoscopic surgery, which can also confirm the diagnosis by microscopical examination.