Burkholderia pseudomallei is endemic in northern Australia, and melioidosis is a common cause of sepsis in the region. We summarized the cutaneous manifestations of melioidosis from a prospective cohort of 486 patients with culture-confirmed melioidosis in northern Australia, and we compared those who had primary skin melioidosis with those who had other forms of melioidosis. Primary skin melioidosis occurred in 58 patients (12%). Secondary skin melioidosis--multiple pustules from hematogenous spread--was present in 10 patients (2%). Patients with primary skin melioidosis were more likely to have chronic presentations (duration, >or=2 months). On multivariate analysis, patients with primary cutaneous melioidosis were more likely to be children aged <or=15 years (adjusted odds ratio, 8.50; 95% confidence interval [CI], 3.24-22.28) and to have a history of occupational exposure to B. pseudomallei (adjusted odds ratio, 3.12; 95% CI, 1.56-6.25) but were less likely to have typical risk factors--including diabetes (adjusted odds ratio, 0.26; 95% CI, 0.12-0.56), excessive alcohol intake (adjusted odds ratio, 0.45; 95% CI, 0.22-0.90), and chronic lung disease (adjusted odds ratio, 0.26; 95% CI, 0.10-0.67). Of those patients with primary skin melioidosis, 1 patient was bacteremic and none had severe sepsis or died from melioidosis. Four (7%) of the 58 patients presenting with primary skin melioidosis had disseminated melioidosis, and 1 (2%) experienced a relapse of melioidosis. Nine patients (16%) were cured with a regimen of oral antibiotics alone, and 1 recovered with no therapy. In our cohort, patients with primary skin melioidosis were younger, had fewer underlying medical conditions, and had better outcomes than did those with other forms of melioidosis. There may be a role for exclusive oral antibiotic therapy for some cases of primary skin melioidosis.