Separation from parents is a key aspect of adolescent development and has been linked to a variety of important mental and behavioral health outcomes. Separation-individuation measures were developed in the United States and have been used in Asian contexts. However, no cross-cultural studies have demonstrated that measures of separation-individuation tap the same domains across Asian and American adolescents. This article describes two studies conducted to develop and initially validate a scale for measuring adolescent separation-individuation. Study 1 (n = 300) developed a Brief Measure of Separation-Individuation (BMSI) using Confirmatory Factor Analysis and Item Response Theory. The result was a 32-item BMSI that provided comparable test information to the original 148-item measure. Study 2 examined the BMSI for measurement invariance and convergent validity across U.S. and Taiwanese samples (ns = 231 and 323). Findings suggest that functional independence, attitudinal independence, and emotional independence may be culturally invariant separation-individuation constructs. However, conflictual independence seems to be more culturally dependent in that its items were only partially scalar invariant and it was only loosely related to the other separation-individuation factors. Findings are consistent with previous research that recommended against using total scores for the PSI (i.e., scoring a single separation-individuation dimension). This study suggests the BMSI holds promise as a brief measure of separation-individuation that can be used in cross-cultural research.