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PubMed This is a summary of 18 peer-reviewed journal articles Updated
Endocrinology

The Thyroid Biopsy and the Bethesda System

At a Glance

A thyroid needle biopsy is reported in one of six Bethesda categories. Benign results are usually monitored, while indeterminate results may lead to a repeat biopsy or molecular testing; suspicious or malignant results often lead to surgery, depending on ultrasound findings and personal factors.

A Fine-Needle Aspiration (FNA) is the standard first-line procedure to evaluate a suspicious thyroid nodule [1]. During the procedure, a doctor uses a very thin needle under ultrasound guidance to collect a small sample of cells from the nodule [2][3].

Most patients find the procedure involves only mild pressure or a “pinching” sensation, and it is usually finished quickly [4][3]. What to expect afterward: You may have mild soreness or bruising at the site. If you experience rapidly increasing swelling or difficulty breathing, contact your care team immediately. If you take blood thinners, your doctor will provide individualized instructions on whether to pause them beforehand.

Afterward, the cells are examined by a cytopathologist under a microscope. It is important to know that while FNA is highly accurate, it is not perfect. There is a small chance of a false-negative result, and FNA cannot distinguish certain types of benign tumors (like follicular adenoma) from their cancerous counterparts (follicular carcinoma) without surgically examining the entire nodule capsule [5].

The Bethesda System: Understanding Your Results

To make biopsy reports clear, doctors use the Bethesda System for Reporting Thyroid Cytopathology. Your result will fall into one of six categories. The malignancy risks and “typical next steps” below are approximate guidelines—your actual plan will depend on your ultrasound, nodule size, and local facility practices [5]:

Bethesda Category Description Meaning Typical Next Step
I Nondiagnostic Not enough cells were collected to make a diagnosis [5]. Repeat the FNA with ultrasound guidance [6].
II Benign The cells look normal. This is the most common result [5]. Monitor with ultrasound (Active Surveillance) [7].
III AUS / FLUS Atypia of Undetermined Significance. Some cells look slightly unusual, but not enough to call it cancer [5]. Repeat FNA or Molecular Testing [8].
IV Follicular Neoplasm The cells are arranged in a pattern that could be a benign tumor or cancer; the microscope cannot tell them apart [5]. Molecular Testing or Diagnostic Surgery (Lobectomy) [9].
V Suspicious The cells look highly suspicious for cancer [5]. Surgery is usually considered, ranging from lobectomy to total thyroidectomy [10].
VI Malignant The cells show features of cancer [5]. Surgery (Total Thyroidectomy or Lobectomy, or rarely active surveillance for very small cancers) [10].

Navigating “Indeterminate” Results (Bethesda III and IV)

Categories III and IV are called indeterminate because the microscope alone cannot provide a definitive answer [5]. Instead of proceeding directly to diagnostic surgery, doctors now often use additional tools to refine the risk.

Molecular Testing

Molecular testing (such as ThyroSeq, Afirma, or others) analyzes the DNA and RNA within your thyroid cells to check for specific genetic mutations [11][12].

  • A “Negative” Result: This test is excellent at lowering the estimated risk of cancer. While it does not guarantee a 0% risk, a negative result often reduces the risk enough that you and your doctor may feel comfortable proceeding with active surveillance instead of surgery [12][13].
  • A “Positive” Result: Finding certain mutations (like BRAF V600E or TERT) increases the concern for cancer. However, a positive result does not universally dictate the extent of surgery. The decision between a lobectomy (removing half the thyroid) or a total thyroidectomy depends on the specific mutation, the nodule’s size, ultrasound features, and your personal preferences [14][10].

The performance of these tests depends heavily on the specific assay used, the local prevalence of cancer, and sample quality.

Repeat FNA

Sometimes, simply repeating the biopsy can provide a clearer answer. Many nodules that were initially Bethesda III are reclassified as Benign upon a second biopsy [15].

What About NIFTP?

You may hear the term NIFTP (Non-invasive follicular thyroid neoplasm with papillary-like nuclear features). This is a very low-risk, borderline tumor that used to be called cancer but is now considered an indolent lesion when strict diagnostic criteria are met [16]. NIFTP generally cannot be definitively diagnosed solely from an FNA biopsy because the entire nodule must be surgically removed and examined to confirm it is not invasive. When the criteria are met, NIFTP is usually treated adequately by complete excision (lobectomy) [17][18].

Common questions in this guide

Is a thyroid FNA painful, and what should I expect afterward?
Most people feel mild pressure or a brief pinching sensation, and the procedure is usually quick. Mild soreness or bruising can occur afterward. Rapidly increasing swelling or trouble breathing requires immediate contact with your care team.
Does Bethesda category II mean my thyroid nodule is cancer-free?
Bethesda category II means the cells look benign and the nodule is commonly followed with ultrasound. It lowers concern for cancer, but your care plan still depends on the nodule’s size, ultrasound features, and clinical context.
What does an indeterminate Bethesda III or IV result mean?
It means the cells do not provide a definite answer about whether the nodule is cancerous. Your clinician may recommend a repeat biopsy, molecular testing, or diagnostic surgery based on the ultrasound findings, nodule size, and your preferences.
What does a negative or positive molecular test mean for my thyroid nodule?
A negative result usually lowers the estimated cancer risk enough that active surveillance may be reasonable, but it does not make the risk zero. A positive result increases concern, yet the choice between removing one thyroid lobe and removing the whole thyroid depends on the mutation, nodule features, and your goals.
What usually happens after a Bethesda V or VI result?
Bethesda V is highly suspicious for cancer, while Bethesda VI shows cancerous features, so surgery is often discussed. Options may include removing one thyroid lobe or the whole thyroid; very small cancers may sometimes be monitored, depending on the individual situation.
What is NIFTP, and can a biopsy diagnose it?
NIFTP is a low-risk borderline thyroid tumor that was formerly classified as cancer in some cases. A needle biopsy usually cannot confirm NIFTP because the entire nodule must be removed and examined for invasion. When strict criteria are met, removal of the affected thyroid lobe is usually adequate treatment.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What is the exact Bethesda category for my biopsy result, and what is the estimated risk of malignancy for that category at this facility?
  2. 2.If my result is Bethesda III or IV, would you recommend a repeat biopsy or molecular testing first?
  3. 3.If we use molecular testing like ThyroSeq or Afirma, how will a 'negative' or 'positive' result specifically change your recommendation for surgery or monitoring?
  4. 4.For an 'indeterminate' result, what features on my ultrasound might make you lean more toward surgery versus waiting?
  5. 5.Is my nodule a 'cold' nodule on a thyroid scan, and how does that factor into our next steps?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (18)
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    A Case of Diffuse Thyroid Hematoma after Ultrasound-Guided Fine Needle Aspiration.

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    The impact of rapid on-site evaluation on thyroid fine-needle aspiration biopsy: A 2-year cancer center institutional experience.

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    A Literature Review of Factors Associated With Pain From Fine Needle Aspiration Biopsy of Thyroid Nodules.

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This page is for informational purposes only and does not constitute medical advice about your multinodular goiter or biopsy. Ask your endocrinologist, surgeon, or pathologist to interpret your Bethesda result and recommend next steps.

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