Skin cancer is caused by DNA damage in skin cells, and the single biggest source of that damage is ultraviolet radiation from sunlight and tanning beds. But UV exposure isn’t the only cause. Genetics, chemical exposures, certain viruses, immunosuppression, and prior radiation therapy all play a role. Around 6.1 million adults in the U.S. are treated for basal cell and squamous cell carcinomas each year, making skin cancer by far the most common type of cancer.
UV Radiation: The Leading Cause
Ultraviolet light damages DNA in skin cells by creating abnormal bonds between neighboring DNA building blocks, called pyrimidine dimers. When these errors aren’t repaired correctly, they become permanent mutations that can push cells toward uncontrolled growth. Two types of UV radiation reach your skin, and they cause harm differently.
UVB radiation (the shorter wavelength, 280 to 320 nm) is the primary driver of mutations in skin cancer. It creates a broad pattern of DNA damage across many types of DNA sequences and is strongly linked to the mutation signatures found in most skin cancers, including melanoma. UVB is also the wavelength responsible for sunburns, which serves as a visible marker of acute DNA injury.
UVA radiation (320 to 400 nm) penetrates deeper into the skin than UVB, reaching the basal layer of the epidermis where melanocytes live. This matters because melanocytes are the cells that become melanoma. UVA causes DNA damage more selectively at specific DNA sequences, and research from Nucleic Acids Research shows the pattern of that damage closely resembles a mutation signature found in melanoma. UVA also passes through window glass and is present at consistent intensity throughout the day, making it harder to avoid than UVB.
Tanning beds emit both UVA and UVB, often at intensities several times stronger than midday sun. Indoor tanning before age 35 significantly raises the risk of melanoma.
Fair Skin and Natural Pigmentation
Your skin’s natural pigment level is one of the strongest predictors of skin cancer risk. The Fitzpatrick scale classifies skin into six types based on how it responds to sun exposure. People with types I and II, those who burn easily and rarely or never tan, face the highest risk. Types V and VI, with naturally dark brown or black skin, have the lowest risk because greater melanin production provides more built-in UV protection.
That said, lower risk is not zero risk. Skin cancer occurs in people of all skin tones and is often diagnosed at later stages in people with darker skin, partly because it’s less expected and harder to spot visually.
Inherited Gene Mutations
Some people inherit gene changes that make their cells less able to suppress tumor growth or repair DNA damage, putting them at elevated risk from birth.
For melanoma, the most well-established hereditary gene is CDKN2A, a tumor suppressor. When this gene is mutated, cells lose a key brake on division. Other genes linked to familial melanoma include CDK4, MITF, BAP1, and POT1. Families carrying these mutations often see melanoma diagnosed at younger ages and in multiple relatives.
For basal cell carcinoma, a condition called basal cell nevus syndrome (also known as Gorlin syndrome) dramatically increases risk. It’s caused by inherited mutations in genes called PTCH1, PTCH2, or SUFU, which normally help regulate cell growth. People with this syndrome can develop dozens or even hundreds of basal cell carcinomas over their lifetime, often starting in their teens or twenties.
Viruses That Trigger Skin Cancer
Two viruses are directly implicated in skin malignancies.
Merkel cell polyomavirus causes the majority of Merkel cell carcinomas, a rare but aggressive skin cancer. The virus inserts its DNA into a host cell’s genome and produces proteins that hijack the cell’s growth controls. One viral protein disables a key tumor suppressor (pRb), forcing the cell into a replication cycle. Another stabilizes cancer-promoting proteins inside the cell, accelerating malignant transformation. The virus must be continuously active to maintain the cancer, meaning the tumor depends on viral gene expression to survive.
Certain strains of human papillomavirus, specifically beta-HPV types 5, 8, and 38, are linked to non-melanoma skin cancers. These strains work differently from the HPV types that cause cervical cancer. Their viral proteins interfere with the cell’s ability to repair UV-induced DNA damage, essentially disabling a safety net that would normally catch mutations before they become dangerous. Interestingly, the virus may only be needed to initiate the cancer. Once enough DNA damage accumulates, the tumor can sustain itself even after the virus is gone, a process researchers call a “hit-and-run” mechanism. These HPV-related skin cancers are especially common in people with weakened immune systems.
Immunosuppression
A healthy immune system constantly patrols for abnormal cells and destroys them before they become tumors. When that surveillance is weakened, skin cancer risk climbs sharply. Organ transplant recipients, who take immunosuppressive drugs for life to prevent rejection, face up to a 100-fold higher risk of developing skin cancer compared to the general population.
The increase is most dramatic for squamous cell carcinoma, which becomes the most common skin cancer in transplant patients (reversing the usual pattern where basal cell carcinoma dominates). People living with HIV, those on long-term immunosuppressive therapy for autoimmune diseases, and anyone with a chronically suppressed immune system also carry elevated risk, though not as extreme as transplant recipients.
Chemical and Industrial Exposures
Several workplace chemicals are established skin carcinogens. Arsenic, whether from contaminated drinking water or occupational exposure, is one of the longest-known causes of skin cancer. Chronic arsenic exposure leads to characteristic precancerous skin changes that can progress to squamous cell carcinoma and basal cell carcinoma years or even decades later.
Coal tar and coal-tar pitch are another proven cause. These substances contain carcinogens including benzene, and they enter the body through skin absorption, inhalation, and ingestion. Workers at foundries, aluminum production plants, coke production facilities, and those handling roofing tar, pavement tar, or coal-tar coatings face the greatest exposure. Coal tar is also found in some medicated shampoos and skin treatments, though at much lower concentrations than industrial settings.
Prior Radiation Therapy
Ionizing radiation used to treat other cancers can damage DNA in surrounding skin, creating a risk of secondary skin cancers years later. A study published in JAMA Network Open found that radiation therapy for breast cancer was associated with a 46% elevated risk of melanoma developing in the treated area. The rarest but most dramatically increased cancer was hemangiosarcoma, a malignancy of blood vessel cells in the skin, which showed a 27-fold increase in risk after radiation therapy.
These secondary cancers typically appear years to decades after treatment. The risk applies to any area of skin that receives significant radiation exposure, not just the breast. If you’ve had radiation therapy, your dermatologist will factor that into your skin screening schedule.
Cumulative Damage and Multiple Factors
Skin cancer rarely results from a single cause acting alone. In most cases, it develops from layers of risk compounding over time. A person with fair skin who works outdoors accumulates more UV-induced mutations per hour of exposure than someone with darker skin doing the same work. Someone with a genetic predisposition who also tans indoors faces a steeper risk curve than either factor would produce on its own. Immunosuppressed patients exposed to beta-HPV strains face a combination that makes skin cancer nearly inevitable without aggressive monitoring.
The practical takeaway is that while UV radiation is the dominant and most modifiable cause, your total risk profile includes your genetics, your immune health, your occupational exposures, and your medical history. Understanding which factors apply to you helps determine how aggressively you should protect your skin and how often you need professional skin examinations.