Objective: Li-Fraumeni syndrome (LFS) is a rare hereditary cancer predisposition syndrome that significantly increases one’s lifetime cancer risk from infancy to late adulthood. LFS is primarily caused by pathogenic autosomal dominant germline TP53 variants. Consequently, each naturally conceived biological child of an individual with a pathogenic variant has a 50% chance of inheriting it. This study examines the connections between family cancer history and reproductive beliefs within multigenerational family units including at least one member with TP53-positive LFS. Method: Forty-five families enrolled in a protocol-specific cancer screening study completed 66 group interviews. An interdisciplinary team constructed a thematic codebook of inductive and deductive codes using interpretive description and modified ground theory to analyze data and then implemented a framework method to organize themes. Results: The following major themes were related to reproductive beliefs in the context of LFS: (a) tension between morality and generational cancer experiences, (b) discriminating between multiple moral frames (i.e., religion and risk reduction), and (c) impossible choices between one’s own health and future children. Conclusions: Reproductive beliefs associated with LFS are distinct from other well-studied hereditary cancer syndromes. Families with LFS experience novel reproductive beliefs that may trigger moral distress. Reproductive LFS-tailored psychoeducational interventions and clinician awareness are needed.