The recent accumulation of epidemiologic and molecular research focused on nonsmall cell lung cancer (NSCLC) in combination with the development of novel/targeted therapies has caused pathologists to critically evaluate the issue of the histologic subclassification of such tumors. The use of the generic term NSCLC, once fully endorsed and accepted by our oncology colleagues, has recently been taken to task, and we are being asked, ''Can you tell if it is a squame or an adeno?'' by our clinical partners on a routine basis. This shift in framework in the diagnostic reporting of lung cancer poses practical challenges in the arena of diagnostic pulmonary cytology. Although cytology is an excellent discriminator of small cell carcinoma versus nonsmall cell carcinoma, it is less reliable in the subclassification of NSCLC. 1 Furthermore, we are being asked to provide molecular-level information on small biopsy specimens (epidermal growth factor receptor [EGFR] gene mutations, KRAS gene mutation, ALK-EML4 gene fusion, etc), which is even more problematic for many cytologic specimens (aspirates, brushes, washes) that may have very limited residual specimen for testing. How does all this impact the day to day sign out of pulmonary cytology specimens? A few points for consideration are presented below. The reader can draw his or her own conclusions, and we will welcome a spirited and critical debate in this journal.1. What are the most important goals of sampling a pulmonary mass via aspiration or exfoliative cytology techniques?The primary goal is to establish, with certainty, the biologic nature of the mass; benign (eg, inflammatory) versus malignant. If a lesion can be placed into the ''malignant'' category, then the second objective is to determine whether it is a primary or metastatic lesion. Ancillary studies, such as immunocytochemistry, can be very helpful in this regard, particularly when the clinical picture is unclear, and are worthwhile uses of residual material. When the lesion is a primary lung tumor, the distinction between small cell and nonsmall cell histology is important for proper classification. These diagnostic objectives have not changed despite the molecular-driven changes in pulmonary oncologic practice.2. What is the clinical significance of distinguishing NSCLC subtypes on cytologic specimens? The principal (albeit not sole) driver of the interest in specifying subtypes of NSCLC in pathology reports is the advent of bevacizumab (Avastin), a vascular endothelial growth factor (VEGF) receptor inhibitor, as a treatment of NSCLC. Briefly, bevacizumab was found to have an unacceptable risk of life-threatening pulmonary hemorrhage in patients who have squamous cell (compared with nonsquamous cell) morphology. Data on