Malassezia are a lipid-dependent basidiomycetous yeast of the normal skin microbiome, although Malassezia DNA has been recently detected in other body sites and has been associated with certain chronic human diseases. This new perspective raises many questions. Are these yeasts truly present in the investigated body site or were they contaminated by other body sites, adjacent or not? Does this DNA contamination come from living or dead yeast? If these yeasts are alive, do they belong to the resident mycobiota or are they transient colonizers which are not permanently established within these niches? Finally, are these yeasts associated with certain chronic diseases or not? In an attempt to shed light on this knowledge gap, we critically reviewed the 31 published studies focusing on the association of Malassezia spp. with chronic human diseases, including psoriasis, atopic dermatitis (AD), chronic rhinosinusitis (CRS), asthma, cystic fibrosis (CF), HIV infection, inflammatory bowel disease (IBD), colorectal cancer (CRC), and neurodegenerative diseases.