This chapter will discuss the ways in which lung cancer histology and location determine its clinical presentation. Hallmark clinical and radiologic manifestations of lung cancer can be organized into three categories: intrathoracic, extrathoracic, and paraneoplastic. Though tobacco use is strongly associated with lung cancer, 10–20% of new diagnoses per year occur in non-smoking individuals. Additionally, patients most at risk for lung cancer may be late to report symptoms, believing them to be inconsequential, secondary to smoking, associated with comorbidities, or as a process of normative aging. Therefore, prompt clinician recognition and thorough evaluation of hallmark symptoms, regardless of smoking status, is crucial to establish an early diagnosis and improve outcomes in all histologic subtypes. This chapter aims to elevate awareness among medical and nursing communities regarding common presenting features of lung cancer to facilitate a prompt diagnosis, improve treatment coordination, support patient well-being, and reduce pretreatment mortality.