Patients with metastatic NSCLC (stage IV disease) usually present with constitutional symptoms (ie, fatigue and weight loss), organ-specific symptoms (ie, bone pain and neurologic symptoms), and/or abnormal laboratory findings (ie, anemia, elevated alkaline phosphatase levels, and/or elevated liver enzyme levels). In many of these patients, a FNA or a needle biopsy of a site of metastasis represents the most efficient way both to make a diagnosis and to confirm the stage. In some cases, however, the metastatic site may be technically difficult to biopsy. If metastatic disease can be predicted with a high degree of accuracy on the basis of radiographic findings (ie, multiple brain, liver, or bone lesions), it may be more efficient to achieve a diagnosis of the primary lung lesion by whatever method is easiest for the patient (ie, sputum cytology, bronchoscopy, or transthoracic needle aspiration [TTNA]). This decision must be made by weighing the technical considerations involved in each approach as well as the reliability of diagnosing an extrathoracic lesion as a site of metastasis based on radiographic appearances alone (see the article on clinical/noninvasive staging elsewhere in this supplement). A joint decision among the radiologist, the pulmonologist, and the medical or radiation oncologist is the desirable approach.