Tremendous progress has been made promoting diversity in recruitment for genomic research, yet challenges remain for several racial demographics. Research has cited intertwined fears of racial discrimination and medical mistrust as contributing factors. This study aimed to identify key factors to establishing trust in medical and genomic screening and research among African Americans and White Americans. Participants completed online focus groups and resulting transcripts were analyzed using a qualitative descriptive approach, with content analysis methods based on recommendations by Schreier. Fifteen African Americans and twenty-three White Americans participated in the study, 63% of which were female. The mean age of participants was 38.5 (SD = 16.6). The Overarching Theme of Trust is Context Dependent was identified, along with the following five themes describing elements influencing trustworthiness for our participants: (1) Professional Experience, Education, and Training Bolster Trust; (2) Trust Depends on Relationships; (3) Cross-checking Provided Information is Influential in Establishing Trust; (4) Trust is Undermined by Lack of Objectivity and Bias; and (5) Racism is an Embedded Concern and a Medical Trust Limiting Component for African Americans. To effectively address mistrust and promote recruitment of diverse participants, genomic research initiatives must be communicated in a manner that resonates with the specific diverse communities targeted. Our results suggest key factors influencing trust that should be attended to if we are to promote equity appropriately and respectfully by engaging diverse populations in genomic research.