Background: Increasingly used for clinical purposes, genome and exome sequencing can generate clinically relevant information that is not directly related to the reason for testing (incidental or secondary findings). Debates about the ethical implications of secondary findings were sparked by the American College of Medical Genetics (ACMG) 2013 policy statement, which recommended that laboratories report pathogenic alterations in 56 genes. Although wide variation in laboratories’ secondary findings policies has been reported, little is known about its causes. Methods: We interviewed 18 laboratory directors and genetic counselors at 10 U.S. laboratories to investigate the motivations and interests shaping secondary findings reporting policies for clinical exome sequencing. Analysis of interview transcripts and laboratory documents was informed by sociological theories of standardization. Results: Laboratories varied widely in terms of the types of secondary findings reported, consent-form language, and choices offered to patients. In explaining their adaptation of the ACMG report, our participants weighed genetic information’s clinical, moral, professional, and commercial value in an attempt to maximize benefits for patients and families, minimize the costs of sequencing and analysis, adhere to professional norms, attract customers, and contend with the uncertain clinical implications of much of the genetic information generated. Conclusions: Nearly all laboratories in our study voluntarily adopted ACMG’s recommendations, but their actual practices varied considerably and were informed by laboratory-specific judgments about clinical utility and patient benefit. Our findings offer a compelling example of standardization as a complex process that rarely leads simply to uniformity of practice. As laboratories take on a more prominent role in decisions about the return of genetic information, strategies are needed to inform patients, families, and clinicians about the differences between laboratories’ practices and ensure that the consent process prompts a discussion of the value of additional genetic information for patients and their families.