5-Fluorouracil (5-FU) Cream

Clearing a sun-damaged field is also a form of prevention, because some actinic keratoses, left alone, can turn into squamous cell carcinoma.⁶ 5-FU is not used for invasive (deeper) skin cancers or melanoma, which need surgery or other treatments.¹

What the reaction looks like

5-FU is supposed to make the treated skin look worse before it looks better. Over the first one to two weeks the area becomes red, raw, crusted, and sometimes sore, right where the sun damage is. This reaction is the treatment working. It then settles over the next couple of weeks as fresh skin comes in.² The reaction can look alarming, but it is expected, and your clinician can tell you how to soothe the skin and when the course is done.

How well it works

The table above summarizes the evidence by condition. The detail below adds the key numbers.

For actinic keratoses, 5-FU is a first-line field treatment. One large trial compared four field treatments. A year later, 74.7% of people stayed clear with 5-FU. The others were lower: 53.9% for imiquimod, 37.7% for photodynamic therapy, and 28.9% for ingenol mebutate gel.³⁷ Major guidelines strongly recommend it.⁸ One honest caveat: spots come back. When the whole treated area was checked at a year, only about a third of people stayed fully clear. So a course is sometimes repeated over time.⁹

Adding a second cream, calcipotriol, for a short 4-day course boosted short-term clearance well beyond 5-FU alone in one trial.¹⁰ A review found this combination also lowered later squamous cell cancers on the face and scalp; in the same research it did not change the rate of basal cell cancers.¹¹¹² 5-FU is also commonly paired with freezing, which can clear more spots than freezing alone.¹³¹⁴

A separate idea is prevention: one short course of 5-FU to the face and ears cut the number of squamous cell cancers needing surgery by about 75% in the first year in a large veterans trial, though it did not lower basal cell cancers and the benefit faded after that first year.¹⁵ It also lowered first-year treatment costs.¹⁶

For Bowen's disease (squamous cell carcinoma in situ), a 250-person trial found 5-FU non-inferior to surgically removing the spot, with a better cosmetic result. About 86% of treated spots stayed clear at both 1 and 4 years, and no squamous cell cancer arose in any treated area over the longer follow-up. Surgery still clears the most spots, so it stays the choice when the priority is the highest cure rate.¹⁷¹⁸ For superficial basal cell carcinoma, 5-FU is an option, but imiquimod tends to clear more (see the table above).¹⁹ For how 5-FU compares with freezing and other creams for actinic keratoses, see the actinic keratosis guide.

Other options patients ask about

People often look for something gentler than the 5-FU reaction, or a "natural" way to avoid it. Here is what the evidence shows.

• Imiquimod, photodynamic therapy, and diclofenac gel are real, proven alternatives. Imiquimod can leave a better cosmetic result and more lasting clearance, but takes a longer course; diclofenac is gentler but clears less.⁹⁸ These belong on their own pages and are worth discussing, but they are reasons to pick a different treatment, not to skip treatment.
• Tirbanibulin is a newer, shorter cream (5 days). In a 2026 trial it cleared about as well as 5-FU short-term and was better tolerated, though its longer-term staying power is less established.²⁰
• Ingenol mebutate (Picato) is no longer available. It was withdrawn from the market after data linked it to more skin cancers in treated areas, and it was the least effective option in the head-to-head trial.³
• Apple cider vinegar and other "natural" topicals have no evidence for clearing precancers, and home acids can burn the skin and hide a growing cancer.
• Black salve and similar corrosive pastes are harmful. They are sold online as a skin cancer cure. But the claims are not evidence-based, and serious injuries have been reported. They can also leave cancer behind under a scab where no one can see it.²¹²²

Why getting the spot checked first matters

5-FU treats the surface. That is the whole reason a diagnosis comes first. A spot that looks like a simple precancer, or a "superficial" basal cell carcinoma, can be something deeper. Studies show deeper cancers are sometimes missed at the start and only found after a cream fails.²³ Treating yourself with a cream, an acid, or a corrosive paste can destroy the tissue a doctor needs to make the diagnosis. It can also let a real cancer grow. A skin exam and, when needed, a biopsy come first.

Who should not use it

5-FU is a prescription medicine with real cautions:

• Pregnancy. 5-FU should not be used during pregnancy, and it is not advised while breastfeeding. Tell your clinician if you are or could be pregnant.
• A rare enzyme deficiency (DPD). A small number of people lack enough of the enzyme that breaks 5-FU down. In them, even a cream can rarely cause serious whole-body effects. Tell your clinician about any past severe reaction to fluorouracil or related chemotherapy.²⁴²⁵
• The Tolak (4%) cream contains peanut oil; ask your clinician if you have a peanut allergy, though the studied product was reported safe in peanut-allergic patients.⁴

When to see a doctor

Call your clinician if the reaction becomes very painful, oozing, or looks infected, if it spreads well beyond the treated area, or if a spot does not heal after the course is finished. And see a clinician before starting any cream on a spot that is new, changing, bleeding, or different from your others, so it can be properly checked first.

Frequently asked questions

Is 5-FU cream chemotherapy? Yes, it is a chemotherapy medicine, but used as a cream it acts mostly on the skin where you apply it, not throughout the body.² That is different from chemotherapy given through a vein.

Why does my skin look so bad while using it? That reaction is the treatment working. 5-FU inflames and clears the sun-damaged cells, so the area gets red and crusted before it heals over a few weeks.²

How well does it work compared with other options? For actinic keratoses, it kept more people clear at one year than imiquimod, photodynamic therapy, or ingenol mebutate in a head-to-head trial.³ Newer tirbanibulin cleared about as well short-term and was better tolerated.²⁰

Can I stop early if the reaction is bad? Talk to your clinician first. Longer courses tend to work better, but a gentler once-daily cream can give a similar result with less irritation, so there may be an easier option than quitting.⁵⁴

Will the spots stay gone? Often not for good. Sun-damaged skin keeps making new spots, so many people need a repeat course over the years.⁹

Can I use a natural remedy instead? There is no proven natural substitute, and corrosive "black salve" pastes are dangerous and can hide a cancer. Get the spot checked and use a treatment that is known to work.²¹²²

Questions to ask your clinician

• Has this spot been examined, and does it need a biopsy before I treat it?
• Which product and schedule fit my skin and my daily routine?
• What should the reaction look like, and how do I care for the skin?
• When should I call you, and when is the course finished?
• Could I or should I be pregnant, and does that change the plan?

5-FU is one of several field treatments. Others include photodynamic therapy and imiquimod, compared side by side in the actinic keratosis guide. The best choice depends on how much sun damage you have, your schedule, and how your skin tolerates treatment. A thorough skin cancer screening is the place to start.

Reviewed by Tyler Long, DO. Last reviewed 2026-06-22.