Cancer randomized clinical trial (RCT) participation is low, particularly among ethnic and racial minorities. Hispanic enrollment is far below their representation in the US population, yet their cancer burden is higher. Little is known from the patient perspective about factors which influence the decision to enroll in RCTs. We asked Spanish- and English-speaking individuals what factors influence decisions about cancer RCT participation. Eight focus groups were conducted with 55 participants (25 Spanish and 30 English-speaking). The groups were taped, transcribed, and analyzed for themes. Six major themes emerged: patient–provider communication, personal relationship with provider, involvement of significant others in decision making, role of faith, need for information, and impact of discrimination on decision making. Both similarities (e.g. need for comprehensive information) and differences (e.g. need for provider acknowledgement of emotional and spiritual concerns) were found between Spanish- and English-speaking participants. Among Spanish-speaking participants, level of education was differentially related to decision-making themes. Implications for providers are discussed.