The purpose of this study is to compare the performance of Afirma GSC and ThyroSeq v.3 in indeterminate thyroid nodules to determine which test can allow more patients to avoid unnecessary surgery and preserve quality of life. In the initial phase of this study, the performance of Afirma GEC and ThyroSeq v.2 were compared.

1. All patients undergoing thyroid FNA within the UCLA Health System will be randomized at the time of FNA to a single molecular test (GSC or ThyroSeq v.3). In the previous phase of the study, patients were randomized to the previous versions of a single molecular test (GEC or ThyroSeq v.2).
2. During the FNA, a sample will be collected for the molecular test.
3. If the cytology results are indeterminate (Bethesda categories 3 or 4), the molecular test will be reflexively sent off.
4. We will help patients with indeterminate thyroid nodules to establish care with an endocrinologist, if they do not already have one. The physicians will make treatment recommendations using best practices and incorporating the results of the molecular test. We anticipate that most patients with a positive molecular test will undergo surgery, while the majority with a negative test will be surveiled.
5. Patients who undergo surgery will have histopathologic evaluation of the thyroid, which will determine whether the index thyroid nodule was benign or malignant.
6. Patients who do not undergo surgery will have a followup ultrasound at 6 and 12 months, or sooner at the discretion of the treating physician.
7. We will assess thyroid-specific quality of life at baseline (following initial diagnosis of an indeterminate thyroid nodule) and during followup (at 6 and 12 months) using the short version of Thyroid-Related Patient-Reported Outcome.

Inclusion Criteria:

• Patients with a thyroid nodule who have a thyroid biopsy performed at UCLA health will be eligible for the study and consented if they agree to participate.
• Patients who have an indeterminate FNA biopsy result (Bethesda category 3 or 4) will be enrolled in the study if they agree to participate.

Exclusion Criteria:

• Patients who do not have an indeterminate biopsy result (either patients who have a benign, insufficient, or malignant result).

Patients undergoing thyroid fine needle aspiration (FNA) within the University of California, Los Angeles (UCLA) Health System