The present mixed methods study developed a comprehensive measure and a screening scale of depression for Chinese American immigrants by combining an emic approach with item response analysis. Clinical participants were immigrants diagnosed by licensed clinicians who worked in the community. Qualitative interviews with clinicians and clinical participants (N = 63) supported the definition of the construct of depression and the development of a 47-item pilot scale. Clinical and community participants (N = 227) completed the pilot scale, measures of neurasthenia and acculturative stress, and the Patient Health Questionnaire Depression Module (PHQ–9). A Rasch partial credit model of 42 items—representing psychological, somatic and interpersonal domains of distress—best fit the data. Twenty-two items overlapped with the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM–IV) symptoms of major depression. Twenty-seven items were biased by acculturation-related variables. Nine items appropriate for self-report screening in primary care and community organizations were chosen to form a brief scale. Both measures showed strong reliability and concurrent and convergent validity. The 9-item scale had better content validity than the PHQ–9. Implications regarding the impact of culture for assessment are highlighted.