Background: Introducing whole genome sequencing (WGS) in pediatric cancer patients at diagnosis poses a unique set of issues. We investigated parental knowledge, attitudes and beliefs about the role of genetics and WGS in the care of children with cancer and towards the return of secondary findings. Methods: Focus groups with parents/caretakers of children with cancer and semi-structured interviews with parents of healthy children were conducted. Participants were recruited from the outpatient pediatric oncology clinic and in-patient units, respectively, at Columbia University Medical Center. The topic guides included questions on genetic research, WGS, secondary findings, and timing of the consent process. All focus groups and interviews were audio recorded, transcribed and analyzed using thematic analysis. Results: 4 focus groups (16 participants (11 females, 5 males; 4 Hispanic, 4 African American, 1 Asian, 10 White)), and 8 semi structured interviews (7 females, 2 males; 4 Hispanic, 3 African American, and 3 White) ranging from high school to graduate school education were conducted. A wide range of knowledge about genetic testing existed among participants; few participants had prior knowledge about WGS. Participants expected that WGS research was more likely to benefit future children rather than their own child. Most participants said they would participate in WGS if there were no additional immediate risks to their child; they wanted to be told about secondary findings but worried about the potential psychosocial burden of those results. There was close to universal opinion that they would not be offering informed consent if asked to participate in WGS at diagnosis and preferred the idea of a two-step consent process. Conclusions: At baseline, parents have very limited knowledge about WGS, regardless of gender, ethnicity or attained education. Parents felt their current level of understanding and perceived level of stress at the time of a cancer diagnosis in their child would hamper the ability to give informed consent. Additional research is required to optimize patient education and timing of the informed consent discussion for WGS.