Medical Oncologist
Biomarker & Molecular Testing
IHC, FISH, PCR or NGS: — Which Test Is Right for Your Cancer?
When your oncologist orders a mutation test, the name on the report can be confusing. Each test looks at a different aspect of your tumour's biology, and the one chosen depends on what treatment decision needs to be made next.
Medically reviewed by Dr. T. Raghavender Reddy, Medical Oncologist, MBBS · DM (Medical Oncology) · MD (Radiation Oncology) · Last reviewed August 2026
- Same tissue, different question — Each test uses your biopsy sample but asks a different question about your tumour's biology.
- Your oncologist chooses, not you — The test ordered depends on the cancer type and the treatment decision immediately ahead.
- Speed reflects purpose — IHC is fast because it answers one specific question. NGS takes longer because it answers many at once.
- Results determine treatment — These tests exist to match you to the treatment most likely to work for your specific tumour.
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Your oncologist chooses between IHC, FISH, PCR and NGS based on what specific change they are looking for in your tumour. IHC and FISH are targeted tests for single markers. PCR confirms one specific mutation. NGS screens for many mutations at once. All four tests use tissue from a biopsy you have already had.
What does each test actually look for?
IHC (immunohistochemistry) applies chemical stains to a thin slice of your tumour and reads the result under a microscope. It shows whether a particular protein is present and in what quantity — for example, whether HER2 is overexpressed in a breast tumour or PD-L1 in a lung tumour.
FISH (fluorescence in situ hybridisation) uses fluorescent probes to look for gene rearrangements or extra copies of a gene — changes that are invisible to an IHC stain. PCR (polymerase chain reaction) amplifies a specific stretch of DNA to confirm whether one known mutation is present or absent.
NGS (next-generation sequencing) reads large sections of your tumour's DNA or RNA in a single run. It can detect the changes the other three tests look for individually, plus many more — which is why it takes longer and costs more.
How do IHC, FISH, PCR and NGS compare?
| Feature | IHC | FISH | PCR | NGS |
|---|---|---|---|---|
| What it detects | Protein presence or level | Gene rearrangements or extra gene copies | One specific known mutation | Many mutations, fusions and copy changes at once |
| How it works | Stained tissue read under a microscope | Fluorescent probes read under a microscope | Amplifies and reads a targeted DNA stretch | Sequences large sections of tumour DNA or RNA |
| Typical turnaround | Fastest — a few working days | Several working days to a week or more | Around one week | Two to three weeks or longer |
| Relative cost | Least expensive | Moderate | Moderate | Highest of the four |
| Common use | HER2, ER/PR in breast; PD-L1 in lung | ALK and ROS1 in lung; borderline HER2 in breast | EGFR, KRAS, BRAF in lung and colorectal cancer | When simpler tests find nothing targetable; clinical trial eligibility; unknown primary |
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MBBS (AIIMS), MS (Surgery) (AIIMS), DNB (Surgical Oncology), MRCS (Edinburgh)
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How does your oncologist decide which test to order?
Your oncologist starts from two things they already know: the cancer type and what treatment decision is immediately ahead. For most breast cancers, that means IHC first — for ER, PR and HER2 — because those three results determine the first treatment plan.
If an IHC result is borderline, FISH is added to confirm it. If the cancer is lung and targeted therapy is being considered, PCR or a small NGS panel may be ordered at the same time rather than waiting for IHC alone.
NGS is usually chosen when simpler tests have not found a targetable change, when the tumour is behaving unusually, or when you are being considered for a clinical trial. It is not the first test by default — it is the test that answers what the others left open.
What does your mutation test result actually mean?
My report says 'not detected' — does that mean no treatment can work?
'Not detected' means the specific change that test was designed to find is not present in your tumour sample. It does not mean all targeted treatments are ruled out — it means this particular marker is not the reason to use them. Your oncologist will look at the full picture, including other markers that have not yet been tested and standard treatment options. If there is any uncertainty, ask which options remain open and whether any further test would clarify them.
Why has my oncologist ordered two tests instead of one?
Because the tests answer different questions. IHC and FISH are often ordered together for HER2 in breast cancer — IHC screens for protein, and FISH confirms the gene amplification when the IHC result falls in the borderline range. Similarly, a lung cancer workup may need IHC for PD-L1 and PCR or NGS for EGFR, because both results lead to different treatment decisions that are not interchangeable. Two tests ordered together are not a sign that something is wrong — they are a sign that two separate questions both need an answer.
NGS takes two to three weeks. Is that delay putting me at risk?
For most cancers, a short wait for NGS results does not affect the outcome of treatment. If your oncologist has a clinical reason to begin something urgently, they will tell you — and in some cases treatment can start on the basis of a faster IHC or PCR result while NGS is still pending. If the wait worries you, ask your team whether any part of your plan can proceed now, and what specific treatment decision the NGS result will determine when it arrives.
Can a blood test replace the tissue biopsy test?
A liquid biopsy — which looks for tumour DNA circulating in the bloodstream — is used in specific situations: most often when a repeat tissue biopsy is not safe or when the tissue sample is too small to test reliably. NCCN guidelines allow it as an alternative in some settings. It is not routinely used instead of tissue testing at the time of first diagnosis, because tissue gives more complete and reliable information. If a liquid biopsy is being considered for you, your oncologist will explain why it is the right choice in your situation.
My tumour tissue sample was small. Will that affect the result?
A small sample can limit which tests are possible and sometimes affects the confidence of the result. When the sample is insufficient, the laboratory will flag this on the report. Your team may then decide whether a repeat biopsy is needed, whether liquid biopsy is a suitable alternative, or whether the result that is available is enough to make the next decision. This is worth asking about directly if your report mentions inadequate sample or limited material.
Did you know?
Some targeted treatments are now approved based on a specific biomarker in the tumour — regardless of where in the body the cancer started. This means an NGS result identifying a qualifying mutation can sometimes open access to a treatment originally studied in a different cancer type.
Your oncologist can tell you whether your biomarker result qualifies for any such tumour-agnostic option.
Source: ESMO Precision Medicine Working Group; NCCN Guidelines (Tumour-Agnostic Indications)
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Common questions
Frequently asked questions
Is NGS always better than IHC or PCR?
NGS is more comprehensive, not automatically better. It answers more questions but takes longer, costs more, and the extra information is only useful if it leads to a treatment decision. For many cancers, a targeted test like IHC or PCR answers the specific question faster and at lower cost. Your oncologist will order NGS when the broader view is genuinely needed, not as a default. If you want to understand why a simpler test was chosen, ask what that test is designed to find and whether NGS would add anything clinically useful in your situation.
Does treatment have to wait until all test results are back?
Not always. Your oncologist can often begin a plan using results that are already available — for example, starting on the basis of an IHC result while NGS is still pending. If a specific result is essential before any treatment can start, your team will explain why. If the wait worries you, ask whether any part of the plan can begin now and what the remaining test result will determine when it arrives.
My oncologist ordered IHC and not NGS — should I ask for more testing?
Not automatically. IHC is the right test for many situations, and ordering NGS when IHC is sufficient adds cost and waiting time without providing clinically useful extra information. The better question to ask is not 'should I have NGS?' but 'has testing identified any targetable change, and are there other markers worth looking for in my cancer type?' Your oncologist can tell you whether the testing done so far covers what is relevant for your diagnosis.
What if my report shows a mutation that my oncologist has not mentioned?
Bring it up directly — show them the report and ask what that result means for your treatment. Mutation reports can include findings at different levels of clinical relevance. Some mutations are classified as variants of uncertain significance, meaning the evidence for their clinical importance is not yet established. Your oncologist will distinguish between findings that change your treatment plan and those that are noted but do not affect it right now. You are entitled to an explanation of every result on your report.
Will I need to be tested again later in my treatment?
Possibly. Tumours can develop new mutations over time, particularly if a targeted treatment stops working. Retesting — from new tissue or a liquid biopsy — is sometimes done to look for changes that explain why the treatment is no longer effective. ESMO guidance supports repeat molecular testing at disease progression in several cancer types. Your oncologist will tell you if and when retesting is relevant in your case.
Do I need to arrange these tests myself?
In most cases, no. Your oncologist orders the tests, the laboratory processes your existing biopsy sample, and the result comes back to your clinical team. If FISH or NGS requires a specialist laboratory, the sample is sent there on your behalf — which is why those tests take longer than IHC. At CION, testing is coordinated as part of your diagnostic workup. The most useful questions to ask are which laboratory is being used and when the result is expected.