Agent Orange Exposure Tied to 31% Higher Odds of Acral Melanoma in Veterans

Agent Orange exposure carries 31% higher adjusted odds of acral melanoma in US veterans, according to a 2026 nested case-control study published in JAMA Dermatology. The association held against veterans with nonacral cutaneous melanoma (adjusted odds ratio, 1.31; 95% CI, 1.06–1.62) and stayed significant against veterans with no melanoma at all — 27% higher adjusted odds (aOR, 1.27; 95% CI, 1.04–1.56).

The paper, "Identification of Risk Factors for Acral Melanoma in US Veterans," drew on Veterans Affairs health care system data collected between 2000 and 2024. Researchers matched 1292 veterans with histologically confirmed acral melanoma to controls diagnosed with either nonacral cutaneous melanoma or no melanoma. That's a large cohort for a rare subtype, and the comparison structure is what gives the exposure signal its weight.

Acral melanoma develops on the palms, soles, and nail units. It is less strongly associated with UV radiation than common cutaneous melanoma, and its origins remain poorly understood. That gap is precisely why the study's authors evaluated a broad set of characteristics: age, sex, race and ethnicity, military branch, smoking status, comorbidities, previous dermatologic conditions, and documented Agent Orange exposure.

One caveat matters up front. This is an observational study. It does not establish a causal association between the herbicide and the disease. It flags a signal, not a mechanism.

What does this change for dermatologists?

For clinicians caring for veterans, the practical shift is simple: military exposure history belongs alongside conventional dermatologic risk assessment. UV-driven risk models don't capture this population well. A documented Agent Orange exposure now sits on the list of factors worth asking about directly.

The findings also sharpen the case for examining acral sites during routine skin screenings — areas easily skipped when the examination focuses on sun-exposed skin. Suspicious findings to watch include changing pigmentation, nail abnormalities, and persistent nonhealing wounds.

That guidance tracks with what patients themselves report. Jessica Scales, PhD, associate director of rare melanoma research at the Melanoma Research Alliance (MRA), described registry data on initial symptoms in a recent Dermatology Times interview: new or changing moles, nail streaks, bleeding, and nonhealing wounds. The soles of the feet were the most frequently reported sites, followed by locations beneath the toenails or fingernails.

"Dermatologists are actually uniquely positioned to monitor these sites during routine skin screenings," Scales said. She also noted that the field is still building its knowledge base: "Researchers are still learning about why acral melanoma develops and its risk factors."

The MRA's RARE Registry, which Scales discussed in the interview and in its 2026 Data Report published July 30, 2026, continues to collect patient-reported data on acral and mucosal melanoma — a resource for clinicians tracking how these rare subtypes actually present.

Other risk factors, and one misleading signal

The study identified additional factors associated with acral melanoma in comparisons with veterans without melanoma, including:

• Previous nevi
• Keratinocyte carcinoma
• Actinic keratosis

Those associations varied depending on the comparison group, which the authors read as a reminder that acral melanoma risk is complex and multifactorial rather than reducible to a single exposure.

One finding demands explicit caution. Current smoking was associated with lower odds of acral melanoma in the analysis. The researchers are direct about what that does and doesn't mean: this observational result should not be interpreted as a protective effect or as any reason to alter smoking-related clinical recommendations.

Acral melanoma also cuts across racial and ethnic populations, unlike UV-associated melanoma, which concentrates in lighter-skinned, high cumulative-exposure groups. That epidemiology reinforces the case for full-body, acral-inclusive screening in every patient rather than risk-stratified shortcuts.

Why the timing lands now

The publication arrives as Veterans Day draws attention to the long-term health consequences of military service. Environmental exposures from decades ago are still generating dermatologic risk data, and the VA cohort studied here spans nearly a quarter century of records.

The study's authors position it as a foundation: further work can now examine Agent Orange exposure and acral melanoma more directly, including the biological pathways that might connect the two. As that research matures, expect military exposure history to move from an afterthought to a standard line in the intake questionnaire for melanoma risk.