Background: To assess melanoma specific health-related quality of life (HRQoL) and health states in patients with earlier stage metastatic (IIIb/c-IVM1a) versus late stage metastatic (IVM1b/c) melanoma. Methods: Data were collected from the Adelphi Real World Advanced Melanoma Disease-Specific Programme, a cross-sectional survey of 112 physicians and their patients (N = 666). Data were collected between March and July 2016 in the US. A subset of 183 patients completed the Functional Assessment of Cancer Therapy Melanoma (FACT-M) and EuroQol-5D (EQ-5D) one time. Patients were classified by stage of melanoma at time of consultation. Descriptive analyses of HRQoL scores between earlier and late stage metastatic melanoma were assessed using Mann-Whitney U tests. Results: The mean age of the earlier stage and late stage metastatic patients was 62 and 64 respectively. More earlier stage metastatic patients had an ECOG status of 0 or 1 versus late stage metastatic patients (85%, 75% respectively). A total of 31% of late stage metastatic patients required caregiver support and had a median time since primary diagnosis of 5.0 months whereas earlier stage metastatic patients reported 14% and 5.2 months respectively. Patients with earlier stage metastatic melanoma had better mean EQ-5D index scores versus late stage metastatic melanoma patients (0.81 (n = 84), 0.76 (n = 93); p = 0.0103). Higher scores indicating better HRQoL were observed between earlier stage metastatic versus late stage metastatic melanoma patients for the FACT-M (120.7 (n = 81), 107.4 (n = 91); p = 0.0017) and subscales (except Social Well Being). Clinically meaningful differences between groups using published minimal important differences (MIDs) were observed in in 6/7 FACT-M subscales and EQ-5D VAS. Conclusions: Differences in HRQoL and health states were observed between earlier stage metastatic and late stage metastatic melanoma populations, highlighting the detrimental effect of developing metastatic disease. These results suggest that treatments that delay progression of the disease are important to conserve patients HRQoL