OBJECTIVES: Health Related Quality of Life (HRQoL) data generated by preference based instruments such as the EQ-5D-5L are highly demanded by policy makers, because they allow for direct comparisons of HRQoL outcomes between disease areas. Such comparisons are scarce in the literature and even fewer are the comparisons between rare and common diseases outcomes. We aimed to assess whether HRQoL outcomes differ between selected therapeutic areas and if so, discuss the aspects that differentiate HRQoL impairment between disease-specific patient populations. METHODS: A web-survey collected data on HRQoL (EQ-5D-5L), self-perceived health (EQ-5D-5L VAS) and disability level (Barthel Index) of Breast Cancer (BC), Rheumatoid Arthritis (RA), Multiple Sclerosis (MS), Rare Cancer (RC) and Rare Disease (RD) patients. 180 patient organisations from 48 countries, were invited to voluntarily share the survey with their members. RESULTS: CONCLUSIONS: When compared to the general population, average utility loss reached 40% for RD and 27% for RA and MS patients, in contrast to 16% and 15% for BC and RC patients respectively, underscoring disease specific differences in HRQoL outcomes and preferences. Future research should also assess the extent to which such differences captured by the EQ-5D can reflect more subtle, clinically relevant differences between patient populations.