Objective: The true prevalence of β-thalassemia is unknown in the United States. Further, basic community knowledge of the disease and its pathogenesis has gone unexplored. The objective of this study was to assess disease knowledge in an at-risk Central Pennsylvanian community, and to assess self-reported carrier frequencies of β-thalassemia. To our knowledge, this is the first assessment of β-thalassemia disease knowledge in an American diaspora of an at-risk patient population. Methods: Participants were recruited in-person at Holy Trinity Greek Orthodox Cathedral in Harrisburg, PA. Permission for the on-site study was received from the Cathedral Dean and Parish Council in writing. Voluntary surveys were administered electronically via RedCap on personal devices and were offered in both Greek and English languages. Inclusion criteria were an age of 13 years and older and the ability to read in Greek or English. Participant demographics were summarized using descriptive statistics. Results: A total of 154 surveys were administered. Of those administered, 140 were completed and met inclusion criteria. Participants with (n = 113) and without (n = 27) Greek heritage were polled. Over 50% of the participants surveyed held a bachelor's degree or higher. Over 64% of all participants did not recognize the term β-thalassemia at all. Over 35% of younger participants (ages 13-44 years) and 34% of older participants (45 years and older) were unaware that the disease could be inherited. Around 50% of all responses were, “Not sure” when asked to identify symptoms of β-thalassemia minor. In order to identify how participants have come to know about the disease, participants were asked about educational sources that have influenced their understanding. Word of mouth was selected as the primary source of education (38.27% in older participants), or no source at all (37.28% in younger participants). Less than 10% of participants between ages 13-44 years had ever learned about β-thalassemia from a medical professional. Participants were asked, “How early can a β-thalassemia diagnosis be made?” Answer choices included “During pregnancy”, “During infancy”, “During childhood”, “Adulthood”, and “Not sure.” Around 45% and 56% of younger and older cohorts, respectively, selected “Not sure”. Out of 140 participants surveyed, 12 (8.57%) responded that they were known carriers of β-thalassemia trait or had β-thalassemia. Eleven reported having β-thalassemia minor (7.85%, Fig. 1), while 1 reported having β-thalassemia intermedia (0.7%, data not shown). When prevalence was re-calculated including only those with self-identified Greek heritage (n = 113), the prevalence of β-thalassemia and intermedia rose to 9.73% and 0.88%, respectively. Conclusion: One of the most concerning gaps uncovered is that there are few sources of educational information (i.e. medical professional, formal education) influencing the knowledge of β-thalassemia in this at-risk population. Self-reported prevalence of β-thalassemia in our cohort is comparable to the national prevalence in Greece (~8%). While The Greek National Prevention Program has been in place since 1974, participants in our cohort responded that “word of mouth” is the main contributing source to their disease understanding. This public health issue is relevant beyond Pennsylvania Greek Americans. In 2017, the global number of refugees reached an all-time high of 25.4 million, including people from regions where β-thalassemia is endemic. It has been noted that the prevalence of β-thalassemia is increasing in North America primarily due to migration. Thus, there is an immediate need to identify, to educate with culturally competent methods, and to screen high-risk communities in the United States.