Understanding Lyme disease testing, false negatives, and clinical diagnosis
What this page covers
This page explains how Lyme disease is tested and diagnosed, why standard tests frequently fail, and how clinical judgment often supersedes laboratory results.
Lyme disease test accuracy is a critical concern for patients and clinicians. Two-tier testing—the CDC-recommended approach—misses many genuine cases, particularly in early infection. Patients with negative tests are often told they don’t have Lyme disease, even when clinical presentation clearly suggests otherwise.
For many patients, the challenge isn’t just having Lyme disease—it’s proving it. Test-based dismissal is one of the most common barriers to appropriate care.
Why Lyme Disease Testing Is So Problematic
Lyme disease tests detect antibodies, not the infection itself. Antibody production takes weeks to months, meaning early testing often returns false negatives. Tests also perform poorly in patients who have been treated with antibiotics, those with immune suppression, and in disseminated or neurologic disease.
The two-tier testing algorithm (ELISA followed by Western blot) was designed for surveillance—not diagnosis. It prioritizes specificity over sensitivity, deliberately accepting false negatives to avoid false positives. This approach serves public health tracking but fails individual patients.
Clinical diagnosis—based on symptoms, exposure history, and response to treatment—remains essential. Many Lyme disease experts diagnose and treat based on clinical presentation when testing is negative or equivocal.
Understanding Test Accuracy & Limitations
Standard Lyme disease tests have significant limitations. Understanding why tests fail helps patients and clinicians make better diagnostic decisions.
- Understanding Lyme Disease Test Accuracy
- How to Test for Lyme Disease: Beyond CDC Guidelines
- Immune Modulating Drug Affects Lyme Disease Test, Delays Diagnosis
- New Lyme Blood Test LymeSeek Promises Earlier, More Accurate Diagnosis
- Can Lyme Disease Trigger a Cascade of Costly, Unnecessary Tests?
- Spinal Tap Leak and Lyme Disease: Worse After Testing
False Negatives & When to Treat Despite Negative Tests
Many patients with genuine Lyme disease test negative. Clinical diagnosis becomes essential when laboratory results don’t match clinical presentation.
- Don’t Wait for a Positive Lyme Disease Test
- Why I Treated Him for Lyme—Even When His Test Was Negative
- Relying on a Negative Lyme Disease Test Can Prove Deadly
- Chinese Man with a Negative Lyme Disease Test: An Inside Lyme Podcast
- Young Child with a “False Brain Tumor” Due to Lyme Disease
- Bell’s Palsy Due to Lyme Disease Misdiagnosed, Patient Bedridden
Two-Tier Testing: ELISA & Western Blot Explained
The two-tier testing algorithm uses ELISA as a screening test, followed by Western blot for confirmation. Understanding this system helps patients navigate test results.
- Save the Two-Tier Lyme Disease Test
- LabCorp to Deny Physicians Access to Western Blot Tests for Lyme Disease
- Video Blog: MOST CHILDREN WITH POSITIVE IGM IMMUNOBLOT FOR LYME DISEASE ARE TRULY POSITIVE
- What is it about the Nanotrap® test we know for Lyme disease that led to support by the Bill and Melinda Gates Foundation?
Misdiagnosis & Delayed Diagnosis
Lyme disease is frequently misdiagnosed or diagnosis is significantly delayed. These cases illustrate common diagnostic failures.
- Chronic Lyme Missed Diagnosis: How Early Cases Slip Through
- Targeted Screening Could Save Lyme Patients from Years of Misdiagnosis
- Lyme Disease Missed Diagnosis: A Case from My Practice
- Early Lyme Diagnosis: Why It Fails and What That Costs
- Lyme Misdiagnosis Apology: When Silence Hurts More Than the Mistake
- Lyme Disease Misdiagnosis in Children: One Family’s Story
- Lyme Rash Misdiagnosis: Not Always a Bull’s-Eye
- Delayed Diagnosis of Lyme Disease in North Carolina
- Study Finds Misdiagnosis and Delayed Diagnosis Common for Lyme Disease Patients
- Lyme Disease Psychiatric Symptoms: A Misdiagnosis Story
- Lyme Disease Was Misdiagnosed as OCD
- Lyme Misdiagnosed as Conversion Disorder in Children
- Lyme Disease Misdiagnosed as Long COVID
- Atypical Findings in Lyme Disease Makes Diagnosing Difficult
- Focus on COVID-19 Leads to Delayed Diagnosis of Lyme Disease
Clinical Diagnosis & Seronegative Lyme Disease
Many patients have Lyme disease without positive antibody tests. Clinical diagnosis becomes essential in these cases.
- Diagnosing Lyme Disease: A Practical Guide for Primary Care
- Ethical Lyme Disease Care: When Clinical Judgment Matters
- Can You Have Neurologic Lyme Disease Even If Your Spinal Tap Is Normal?
- Lyme Endocarditis Diagnosed by PCR Testing
- Culture Evidence of Lyme Disease in Antibiotic Treated Patients Living in the Southeast
- She Was Told It Was Aging—it Was Lyme All Along
- Dismissing Chronic Lyme Disease for Somatic Symptom Disorder Diagnosis
Co-infection Testing
Babesia, Bartonella, and Borrelia miyamotoi are common Lyme co-infections that require separate testing.
- Babesia Testing Errors Can Delay Treatment
- Why I Treat Babesia Even if the Tests Are Negative
- Untreated Babesia: When a Positive Test Leads to No Treatment
- Babesiosis Causes False-Positive HIV Test Results
- Babesia Clinical Diagnosis: When Lab Tests Fall Short
- Delayed Babesia Diagnosis: Why Follow-Up Visits Matter
- Babesiosis Missed Diagnosis: Why Co-infections Have Dire Consequences
- Babesia Underscreening: Why Only 5% of Tick Patients Get Screened
- Night Sweats Babesia: The Symptom Doctors Miss
- Fatal Babesia: A Family’s Story of Delayed Diagnosis
- Congenital Babesiosis: Two Infants, Two Mothers with Lyme
- Borrelia Miyamotoi Diagnosis: Challenges for Clinicians
- Borrelia Miyamotoi Test: CR Peptide May Indicate Infection
- Borrelia Miyamotoi in Canada: Study Finds 10% Infection Rate
- Borrelia Miyamotoi DNA Test: New Sequencing Method
- What is Borrelia Miyamotoi? Symptoms, Diagnosis, Treatment
- Babesia Urban Case: A Walk in the Park Leads to Diagnosis
- Babesia Lyme Co-infection: When One Diagnosis Hides Another
- Rocky Mountain Spotted Fever Diagnosis: Clinical Challenges
Tick Testing
Testing ticks for Lyme disease and co-infections can provide useful information but has limitations.
- Can a Tick Be Tested for Lyme Disease?
- How to Test for Lyme Disease Using a Tick
- No Commercial Diagnostic Tests Available for Emerging Tick-Borne Diseases
- Most Cases Consistent with Lyme Disease Are Not Tested in Non-Endemic Region
Pediatric Diagnosis
Diagnosing Lyme disease in children presents unique challenges.
- Pediatric Lyme Disease Diagnosis Without a Tick Bite
- Pediatric Lyme Disease: Why Children Are Misdiagnosed
- Understanding Pediatric Lyme Disease
- Diagnosing Lyme Arthritis of the Hip in Children
- Lyme Arthritis Symptoms in Young Child Emerge Years After Tick Bite
- Young Kids and the Elderly in New Hampshire Are at Greatest Risk of a Tick Bite
- Only a Minority of Children with Lyme Disease Recall a Tick Bite
- Could There Be Subclinical Cardiac Involvement in Early Lyme Disease in Children?
Additional Diagnostic Resources
Other important testing and diagnostic considerations.
- When Lyme Disease Causes a Positive Test for Mononucleosis
- Lyme Carditis Diagnosis – 18 Cases
- Lyme Carditis Diagnosis During a COVID-19 Quarantine
- Abnormal MRI Leads to Lyme Encephalitis Diagnosis
- One Year After Infection, Patient Shows Signs of Lyme Meningitis
- Lyme Myocarditis in Patient with No Other Signs of Lyme Disease
- Clinical Presentation of Lyme Disease in Patients Living in Germany
- Autopsy Finds Lyme Disease Spirochetes in Patient with Lewy Body Dementia
- Borrelia Antibodies Found in Patients with Coronary Heart Disease
- Case Report: Lyme Neuroborreliosis Triggers Multiple Strokes
- Atypical Case of Lyme Carditis in Florida Woman
- Lyme Disease Presents as Brachial Plexopathy and Meningitis
- Increasing Spread of Lyme Disease in Europe
- Gender Bias in Lyme Disease
- Could Race Affect the Diagnosis and Treatment of Lyme Disease?
- Lyme Disease and Medical Gaslighting: A Barrier to Care
- Do I Have Lyme Disease?
- How Do You Know If You Have Lyme Disease? Key Signs
- Spinal Taps for Lyme Disease: Do You Really Need One?
- Tick Bite Treatment Options: Wait or Treat?
- Single Dose Doxycycline For Tick Bite – Ethical Concerns
- Getting the Diagnosis Correct and Avoiding ‘Anchor Bias’
- Breaking the Groundhog Day Cycle in Chronic Illness
- Preventing Long-Term Lyme Disease
- Does Lyme Disease Go Away? What Recovery Looks Like
- The Ethical Cost of Dismissing PTLDS
- Chronic Lyme Disease Controversy
- I Never Learned About Lyme Disease in Medical School
- Unexpected Relief from Allodynia: Lyme Disease Treatment Worked!
- Case Reports: Lyme Disease Infection Causes Carditis
- Bartonella and Lyme Disease Mimics ALS and MS
- Anaplasmosis and Lyme Disease: Cardiac Complications
- Pregnancy, Breast Feeding and Lyme
- Can Lyme Disease Cause Seizures?
- COVID-19 Long-Haulers and Lyme Disease Patients Share Similar Frustrations
Frequently Asked Questions
Can Lyme disease tests be negative even when you have Lyme?
Yes. Two-tier testing frequently returns false negatives, particularly in early infection, after antibiotic treatment, or in disseminated disease. Clinical diagnosis becomes essential when testing fails.
What is two-tier testing?
Two-tier testing uses ELISA as a screening test, followed by Western blot for confirmation. This algorithm was designed for surveillance and prioritizes specificity over sensitivity, deliberately accepting false negatives.
Should I get tested if I don’t remember a tick bite?
Yes. Most Lyme disease patients don’t recall a tick bite. Testing should be based on symptoms and exposure risk, not tick bite recall.
Can doctors diagnose Lyme disease without positive tests?
Yes. Clinical diagnosis—based on symptoms, exposure history, and response to treatment—is medically appropriate when testing is negative or equivocal.
