ABSTRACT: Importance:Given recent evidence of overdiagnosis and overtreatment of small papillary thyroid cancers (PTCs) and other low-risk cancers, strategies are needed to help patients consider less invasive treatment options. Objectives:To determine which factors influence treatment preferences for patients with PTC, and the trade-offs in treatment factors people are willing to accept, and to understand how terminology influences preferences and benefit-harm trade-offs. Design, Setting, and Participants:Preferences in PTC treatment were evaluated using a discrete choice experiment (DCE) conducted as a web-based survey using an existing public online research panel. Participants were randomized to receive 1 of 2 frames of information based on the terminology used to describe the condition: "cancer" or "lesion." Participants chose between 3 treatment options for PTC (thyroidectomy, hemithyroidectomy, and active surveillance). Analyses were conducted using a mixed logit model. Main Outcomes and Measures:The main outcome variable was treatment preference; attributes of treatment options and sociodemographic characteristics were explanatory variables. Results:The DCE was completed by 2054 participants (993 [48.3%] men and 1061 [51.7%] women; mean [SD] age, 46.0 [16.5] years) with no history of thyroid cancer. Participants preferred options with less frequent follow-up, lower out-of-pocket costs, lower chances of having voice and calcium level problems, and a lower risk of developing invasive thyroid cancer and of dying of thyroid cancer. When trading benefits against harms, participants were willing to accept a higher number of extra patients experiencing adverse effects to avoid a thyroid cancer death when the condition was described as a cancer compared with a lesion. Specifically, participants for whom the condition was described as a cancer were willing to accept more patients requiring lifelong medication (mean, 273; 95% CI, 207-339 vs mean, 98; 95% CI, 66-131), experiencing calcium problems (mean, 110; 95% CI, 77-144 vs mean, 56; 95% CI, 55-58), and fatigue (mean, 958; 95% CI, 691-1224 vs mean, 469; 95% CI, 375-564). For both the cancer and lesion terminology, health literacy consistently was associated with preferences for treatment options. Those with lower health literacy had a significantly lower preference for less invasive treatment options. Conclusions and Relevance:This study makes an important contribution to understanding how attributes of treatment options, terminology, and patient characteristics, in particular health literacy, influence treatment decision making for PTC. As a result of increasing evidence of the indolent nature of PTC and other low-risk cancers, strategies to deal with potential overtreatment are critically needed. Trial Registration:Australian New Zealand Clinical Trials Registry: ACTRN12617000066381.