Asthma and chronic obstructive pulmonary disease (COPD) can present as unique conditions or as a combination known as asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS). These condition(s) can be categorized as obstructive conditions, causing inflammation of small airways leading to decrease airflow, mucus production, and bronchoconstriction. Asthma and COPD affect every age, gender, ethnicity, and socioeconomic status, thus increasing mortality and morbidity burden in our society. Fractional exhaled nitric oxide (FeNO) is an endogenous gaseous molecule which can be measured in the human breath test because of airway inflammation. It has been studied extensively as a marker of inflammation and has been incorporated into an algorithm for asthma management. The purpose of this study was to investigate whether FeNO testing can lead to a change in the diagnosis. A retrospective chart review of 95 patients with asthma, COPD, and ACOS was performed, and FeNO levels were recorded. Out of 95 patients, 36%, 24%, and 22% of the patients had an initial diagnosis of asthma, COPD, and ACOS, respectively. After the FeNO testing, the number of patients with the final diagnosis of asthma and ACOS increased, and COPD decreased. Our results support the utility of FeNO as a viable marker in diagnosing and managing complex cases of asthma, COPD, and ACOS.