To assess rural-urban and health professional shortage area (HPSA)-related influences on the characteristics of melanoma in North Carolina. We conducted a single-center retrospective cohort study of patients living in North Carolina with an available pathology report for invasive cutaneous melanoma seen in the Duke University Health System from 01/01/2014 to 12/31/2020. Multivariable logistic regression models were employed to compare patient and tumor characteristics between rural versus urban county residence as well between melanoma thicknesses dichotomized into thin (≤1.0mm) and thicker (>1.0mm) tumors. The cohort included 807 patients, and rural patients accounted for 177 (21.9%) of invasive cutaneous melanomas. Rural patients had significantly higher odds of having thicker tumors than urban patients (odds ratio [OR] = 1.78, 95% confidence interval [CI]: 1.17-2.71; P =.008). Rural patients were significantly more likely to be female (OR = 1.59, 95% CI: 1.10-2.28; P =.013) and located in a population-based (OR = 2.66, 95% CI: 1.84-3.84; P<.001) or geographic-based (OR = 8.21, 95% CI: 3.33-20.22; P<.001) HPSA. Living in a medium- or high-shortage population-based HPSA was associated with higher odds of thicker tumors (OR = 2.65, 95% CI: 1.85-3.80; P<.001). Patients living in rural North Carolina counties were more likely than those in urban counties to be diagnosed with melanomas >1.0mm in thickness, a clinically significant difference with important prognostic implications. Interventions at the county- and state-level to address this disparity may include improving access to skin cancer screening and teledermatology programs, increasing partnerships with primary care providers, and targeting interventions to counties with health professional shortages.