Key PointsQuestionIs weight loss associated with a diagnosis of lung cancer, whether this loss is recorded by primary care clinicians or by objective measurements?FindingsThis case-control study analyzed data from 2012 through 2019 on 625 patients aged 40 years or older with a first primary lung cancer diagnosis, and 4606 controls matched by age, sex, and smoking status in a US ambulatory care medical system. Patients with lung cancer diagnosis had statistically significant greater odds of weight loss in the previous 6 months than matched controls.MeaningThese results suggest that weight loss may be associated with incident lung cancer among patients, demonstrating a potential opportunity for early diagnosis.