Personalismo may have a broad influence on the well-being of U.S. Latinos by shaping social networks and, in turn, access to information and resources. However, research on personalismo is currently constrained by the lack of a psychometrically sound measure of this cultural construct. This research used a mixed-methods approach to develop a personalismo scale across three studies: a cognitive interviewing study with Mexican American adults (n = 33); a cognitive interviewing study with non-Latino White, Mexican American, Puerto Rican, and Cuban American adults (n = 61); and a psychometric telephone survey with Mexican American, Puerto Rican, and Cuban American adults (n = 1,296). The final, 12-item scale had high internal consistency reliability and appears to be appropriate for use with Mexican American, Puerto Rican, and Cuban American adults. Significant differences emerged across Latino subgroups, with higher personalismo observed among Cuban Americans and female respondents, providing empirical evidence of cultural heterogeneity among U.S. Latino populations.