July 2, 2025 – Amy Jardon couldn't stand it any longer – the incessant itching between her toes.
She saw her primary care doctor, who said the itching and small black spot in the same area were "nothing" but ordered a biopsy just to be safe. Two weeks later, Jardon got a call. It wasn't nothing – it was melanoma. The then-40-year-old runner from Iowa had skin cancer between her toes.
As sunscreen sales surge and more people focus on shielding their skin from those harsh summer UV rays, experts warn that some of the most dangerous skin cancers are not caused by sun overexposure. Every year, thousands of Americans are diagnosed with rare forms of melanoma and other skin cancers that develop in areas that rarely see the sun – like the eyes, mouth, throat, anus, and genitals.
Jardon's diagnosis was acral melanoma, a subtype that affects between 2,000 and 3,000 Americans annually. It appears in places like the soles of your feet, the palms of your hands, and the nail beds of fingers and toes.
While scientists are still uncovering the causes of these seemingly non-sun-related skin cancers, emerging data on acral melanomas shows they have a unique genetic structure – a finding that could be key to not just prevention but also better treatment.
In the meantime, patients like Jardon are banding together to raise awareness: Anyone can get these mysterious skin cancers, even you. Here's what to know.
What the Research Shows
Melanomas are a group of cancers that develop in melanocytes, the cells that produce melanin and give skin its color. Melanoma is highly treatable if caught early, but in later stages, it's one of the deadliest cancers due to its ability to metastasize (spread) to vital organs like the lungs and brain.
Like acral melanoma, mucosal melanoma shows up in parts of the body not typically exposed to the sun, like inside the nose, throat, mouth, and genitals. Uveal melanoma, the most common eye cancer in adults, starts in the uvea (the pigmented layer of the eye) and has no known link to sun exposure. Even basal cell carcinoma cases – typically a sun-related skin cancer – can develop in areas generally protected from the sun, with some estimates suggesting this happens in up to 20% of cases.
All of these often go unnoticed and are diagnosed late, making them more dangerous.
"If people have a black stripe on their fingernail or a lesion on their foot, cancer is not the first thing [they think] about," said Keiran Smalley, PhD, director of the Donald A. Adam Melanoma and Skin Cancer Center of Excellence at Moffitt Cancer Center.
Worse: Acral melanoma is "a lot less responsive" to available treatments, said Smalley.
While more research is needed to understand exactly why, experts point to the cancer's unique mutations. With cutaneous melanomas – the kind clearly caused by the sun's UV (ultraviolet) rays – there are tons of mutations, said Carla Daniela Robles-Espinoza, PhD, a melanoma expert at the National Autonomous University of Mexico, Juriquilla campus.
"But with acral melanoma, the genome is completely different," she said. Instead of lots of small mutations, there are big changes in the structure of DNA. A single gene can be copied over and over – perhaps 50 times. These mutations suggest sun exposure is not the cause.
Another theory: Acral melanoma may be caused by mechanical stress or injury. A few studies have shown that it's more common on pressure-bearing parts of the foot – the heel and ball. This may lead to inflammation, producing DNA-damaging molecules called reactive oxygen species, Robles-Espinoza said.
The Role of Ethnicity and Skin Tone
Acral melanoma can be especially sneaky for people of color.
"I always thought of melanoma as a White person's disease," said Trena Brown, 76, a Black woman from Baltimore who has had three acral melanomas since 2013.
First, a blister-like lesion was removed from her big toe. When the lesion returned, she had her big toe amputated. Then in 2016, a chest X-ray showed the cancer had metastasized to all four corners of her lungs.
"When they tell you you have cancer in your lung from the melanoma on your toe – I can't even describe what that's like," Brown said. She finished an intense round of immunotherapy in 2018 and now gets regular MRIs of her brain, since that's where melanoma often spreads next.
Although acral melanoma accounts for only 2% to 3% of melanoma diagnoses in the U.S., it's responsible for more than half of cases in non-White people. It's the most common type of melanoma in people of African, Asian, and Hispanic descent, Robles-Espinoza said.
Still, that doesn't mean White people are not at risk – data shows they have the same incidence of acral melanoma as other ethnicities, Robles-Espinoza said.
Anyone, regardless of skin tone, can get skin cancer anywhere on the skin, Smalley said.
Looking for More Information
As is the case with other rare diseases, acral melanoma lacks data.
Surgery is the primary treatment – cancerous tissue and some of the bordering healthy tissue are removed – sometimes followed by radiation.
For advanced cases like Brown's, doctors may also rely on immunotherapy, chemotherapy, or targeted therapy aimed at the tumor's genome. All of these were tested and approved for cutaneous melanoma. To date, no treatments have been approved specifically for acral melanoma. Despite growing research, still only seven clinical trials are underway for acral melanoma, compared to 61 for cutaneous melanoma.
The reasons are complex. One challenge is finding enough people for robust trials. Plus, countries that set the agenda for melanoma research – like the U.S., Australia, and the U.K. – are mostly White, Robles-Espinoza said. And they focus on the UV-related skin cancers more common among their populations. Advocacy groups are working to close the gap, creating registries of acral and mucosal melanoma patients to give researchers and doctors more data.
Risk factors are also still emerging. There are no signs that acral or mucosal melanoma risk is inherited, though families at high risk of cutaneous melanoma may also be at higher risk of acral melanoma, Smalley said. Some data suggests acral melanoma risk is higher in people who generally have more moles. It could be that the melanocyte proliferation pathway is already activated in these people, "predisposing them to melanoma," Robles-Espinoza said.
For now, Smalley and Robles-Espinoza agree, the best strategy is to be mindful. Pay attention to your skin (even weird places like between your toes) and don't hesitate to have suspicious spots checked out.
While the itching that drove Jardon to the doctor led to an early (stage I) diagnosis – today, 10 years later, she remains cancer-free – many acral melanomas are subtle, easy to miss, and different from typical skin cancer. The Melanoma Research Alliance recommends the acronym CUBED to assess a spot or mole for acral melanoma:
- Colored: Any part of the lesion is a different color than the skin.
- Uncertain: It's unclear what the lesion is.
- Bleeding: The lesion bleeds or oozes fluid.
- Enlargement: The spot gets bigger or worse despite treatment.
- Delay in healing: The lesion hasn't healed for two months.
Don't assume all doctors will be familiar with acral melanoma. "You have to be your own advocate," Jardon said. And if you're diagnosed with acral or mucosal melanoma, "see a melanoma specialist. They're there for you."
