Background: New genomic markers will increasingly inform clinical care, but some may become available to patients prior to clinical validation. Studies have shown that CYP2D6 is a critical enzyme in the metabolism of tamoxifen and potentially a key determinant in breast cancer outcomes. Our study sought to examine patients’ beliefs about how CYP2D6 genotype would affect their prognosis. Methods: In LCCC 0801, women on tamoxifen for prevention or treatment of breast cancer underwent CYP2D6 genotyping; we increased tamoxifen dose in patients with any intermediate or poor metabolizing (IM or PM) alleles, but not in patients homozygous for extensive metabolizing (EM) alleles. The informed consent said that the purpose of the study was to see if dose adjustment could raise endoxifen concentrations in reduced metabolism patients, but that it is not clear whether this would provide clinical benefit. In an embedded sub-study, 321 patients (84% of possible responders) completed a survey (6 hypothetical vignettes) prior to receiving their genotype. We experimentally manipulated the vignettes to describe whether women hypothetically received tamoxifen treatment (no or yes) and their hypothetical genotype (EM, IM, PM). The outcome was women’s perceived risk of breast cancer recurrence (0% to 100%). We analyzed the data using repeated measures ANOVA to account for the study design. Results: Women expected that tamoxifen treatment would lower their recurrence risk (RR) from 49% to 31% (p<.001). Women believed that genotype would have a small effect on their RR if tamoxifen was not prescribed (46% EM, 48% IM and 53% PM, p<.001). However, they believed that, if they took tamoxifen, genotype would have a substantial effect on their RR (22% EM, 30% IM and 40% PM, p<.001). Conclusions: Women understood that tamoxifen reduced breast cancer risk, but despite study material that described uncertainty about CYP2D6 benefit in clinical-decision making, believed that this benefit was likely to be larger for extensive tamoxifen metabolizers. Though patients are receptive to genomic risk information, the rapidly changing nature of the science calls for caution when communicating clinical utility and results of novel genomic assays.