Transthoracic fine needle aspiration (FNA) biopsies performed under computed tomography (CT) scan (CT-FNA) have greatly improved the cytodiagnosis of lung tumors. However, the distinction between a primary lesion and a metastatic lesion still may be difficult on the basis of morphologic criteria. To evaluate whether a selected panel of monoclonal antibodies (MoAb) to tumor-associated antigens (TAA) can improve the diagnostic potential of FNA, we have immunocytochemically analyzed 122 pulmonary CT-FNA. Whereas conventional cytology was capable of recognizing only the neoplastic nature of the lesions, the immunocytochemical diagnosis could identify the primary or metastatic nature of the pulmonary masses in 92.5% of the cases. The immunocytochemical findings were confirmed by clinical-histopathologic data. The current results demonstrate that the use of immunocytochemical methods can significantly improve the diagnostic accuracy of conventional cytology of lung masses.