INTRODUCTION: The use of molecular tools to individualize health care, predict appropriate therapies, and prevent adverse health outcomes has gained significant traction in the field of oncology under the banner of “personalized medicine” (PM). Enthusiasm for PM in oncology has been fueled by success stories of targeted treatments for a variety of cancers based on their molecular profiles. Though these are clear indications of optimism for PM, little is known about the ethical and social implications of personalized approaches in clinical oncology. OBJECTIVE: The objective of this study is to assess how a range of stakeholders engaged in promoting, monitoring, and providing PM understand the challenges of integrating genomic testing and targeted therapies into clinical oncology. METHODS AND MATERIALS: The study involved the analysis of in-depth interviews with 117 stakeholders whose experiences and perspectives on PM span a wide variety of institutional and professional settings. RESULTS: Despite their considerable enthusiasm for this shift, promoters, monitors, and providers of PM identified 4 domains that provoke heightened ethical and social concerns: (1) informed consent for cancer genomic testing, (2) privacy, confidentiality, and disclosure of genomic test results, (3) access to genomic testing and targeted therapies in oncology, and (4) the costs of scaling up pharmacogenomic testing and targeted cancer therapies. CONCLUSIONS: These specific concerns are not unique to oncology, or even genomics. However, those most invested in the success of PM view oncologists’ responses to these challenges as precedent setting because oncology is farther along the path of clinical integration of genomic technologies than other fields of medicine. This study illustrates that the rapid emergence of PM approaches in clinical oncology provides a crucial lens for identifying and managing potential frictions and pitfalls that emerge as health care paradigms shift in these directions.