Unlike other preventable cancers for which mortality rates are dropping, melanoma mortality has only recently stabilized owing in large part to the unremitting increases among middleaged and older white men, for which much attention has been paid. Gamba et al 1 now focus our attention on young adults.Concentrating on US individuals from the National Cancer Institute's Surveillance, Epidemiology, and End Results registry ages 15 to 39 years, they reveal a rather striking disparity: young men experience a 55% difference in melanoma survival compared with young women. There are many notable findings; among these, sharp sex differences in case fatality wherein young men comprise only 40% of all cases but more than 60% of all deaths. The consistency of the effect seen in 18 registries and over 20 years is quite dramatic; within all specific age groups and across all tumor thickness categories, histologic subtypes, and anatomic sites, young men experience a disproportionate burden of melanoma deaths. Similar sex disparities apparently exist in survival by the presence and extent of regional spread of disease. The findings are so consistent that they imply a fundamental biological difference in "male" vs "female" melanoma, at least for a significant fraction of patients. It is notable that the newly diagnosed melanomas were on average thicker and more advanced in men than in women. This leads to the question of whether increased mortality may have arisen from diagnostic challenges such as "missed" deep margins or later diagnosis and delay. Yet even for melanomas deeper than 4 mm, men fared more poorly than women, thereby pointing more in the direction of distinctive biology. Still, prognosis for disease with distant metastasis was essentially equally poor for men and women.Gamba et al 1 review many of the likely behavioral and biological factors responsible for these sharp disparities. Behavioral factors include women's greater propensity to examine their own skin, their opportunities for receiving medical and preventive care, and the facileness with which they engage physicians in discussions about preventive care or request skin examinations within a routine visit to their primary care physician. [2][3][4] These factors all compete as possible reasons for this disparity, but factors related to tumor biology may come into sharper relief for younger people who make fewer visits to primary care physicians who are well known to discover thinner melanoma than the patient or their significant other.Where might biological differences in male vs female melanoma arise? An obvious possibility could be distinctive exposure patterns to UV radiation. It is likely that both UVdependent plus UV-independent risk factors combine to determine an individual's melanoma risk. UV-independent factors may involve pheomelanin-related carcinogenic propensity, as recently reported in animal models, 5 but current data have not evaluated whether this is a sex-specific process. In addition, further work is needed to determine whether such sex diff...