Lung cancer is the most frequent malignant tumor worldwide, with an estimated 900,000 new cases each year among men and 330,000 among women (12.3% of all cancers, excluding nonmelanoma skin cancers).1Lower respiratory tract cytology is a diagnostic cornerstone for the evaluation of clinically and radiologically suspect pulmonary changes. The combination of cytology and histology leads to a correct diagnosis in > 85% of lung carcinomas.2–4 Nevertheless, it can be difficult or impossible to reliably distinguish reactive atypia from malignant cells based on cytology alone. Reactive atypia occurs in different conditions of lung injury, including chronic bronchitis, infections, diffuse alveolar damage, infarction, and toxicity. All cell types of the respiratory tract can demonstrate worrisome reactive features. Dangerous diagnostic pitfalls that can mimic adenocarcinoma include reactive type II pneumocytes, reactive bronchial epithelial cells, and pulmonary macrophages. Similarly, reserve cell hyperplasia can raise suspicion of poorly differentiated non-small cell lung cancer (NSCLC), and atypical squamous metaplasia may provoke a diagnosis of squamous cell cancer (SCC).5–11 Taken together, equivocal cytology leaves both patients and physicians in uncertainty and can cause unjustified fears or a delay in lung cancer diagnosis.