Background: Cultural factors influence how individuals define, evaluate, and approach their quality of life (QoL). The CushingQoL is a widely used disease-specific questionnaire to assess QoL in patients with Cushing’s syndrome. However, there is no information about potential crosscountry differences in the way patients interpret the items on the CushingQoL. Thus, the current study examined if the CushingQoL is interpreted in the same way across nationalities. Methods: Patients from the U.S. (n = 260) and the Netherlands (n = 103) were asked to fill out the CushingQoL and a short demographics survey. Measurement invariance testing was utilized to explore whether or not the patient samples from the U.S. and the Netherlands interpreted items on the CushingQoL in the same way. Results: A two-subscale scoring approach was used for the CushingQoL. Model fit was good for the U.S. sample (e.g., CFI = 0.983; TLI = 0.979), as well as the Dutch sample (e.g., CFI = 0.971; TLI = 0.964). Invariance testing revealed that three of the 12 items on the CushingQoL were interpreted differently across the groups. These items are all related to psychosocial issues (e.g., irritable mood and worrying about one’s health). Items assessing physical aspects of QoL did not vary across the U.S. and Dutch samples. Conclusions: Interpreting results from the CushingQoL requires careful consideration of country of residence, as this appears to impact the interpretation of the questionnaire.