The evaluation of mediastinal and hilar lymph nodes for tissue diagnosis and staging of lung cancer is now commonly performed by minimally invasive, nonsurgical procedures such as computed tomography-guided fine-needle aspiration and endobronchial ultrasound-guided transbronchial needle aspiration. Ensuring that a sufficient quantity of cellular material has been acquired to enable multiple studies has become a priority issue in the era of personalized medicine, especially for patients with lung cancer, and this can be accomplished by rapid onsite evaluation (ROSE). This commentary focuses on the use of ROSE in guided procedures, especially for hilar and mediastinal lymph node aspirates, and describes an algorithm for handling these specimens.