Although Chinese American Immigrants are the fastest growing Asian subgroup in the United States, social and behavioral research on this particular group is limited due to a variety of barriers. This study aimed to encourage researchers to overcome the barriers associated with performing qualitative cultural research with Chinese American Immigrants. The objectives of this study were to 1) discuss the challenges of conducting qualitative cultural study with Chinese American immigrants, 2) describe lessons learned from qualitatively interviewing Chinese American immigrant communities in the Southeastern area regarding their perspectives about family history and genetic testing, and 3) provide recommendations and suggestions regarding this type of research methods. Since September 2008, we have conducted genomic study of Chinese American immigrants in two major Chinese American immigrant communities in the Southeastern area. A total of 46 Chinese American immigrants participated in our study. This qualitative cultural study highlighted numerous significant and unanticipated challenges that emerged from various aspects of the study, including the IRB review process, informed consent, participant recruitment, community engagement, interview guide development, data collection, data analysis (with qualitative data analysis software), data interpretation, publication, and funding challenges. Potential strategies for dealing with these challenges and future recommendations are discussed. Our experience may help researchers conduct qualitative cultural research not only with Chinese American immigrants but also with other ethnic minority groups, ultimately reducing health disparities in the United States.Keyword(s): health promotion, interdisciplinary, multiculturalism/cultural diversity