The aim of this study was to identify and characterize aetiological and predisposing factors in denture-related stomatitis (DRS), by means of a case-control, transversal study, in a large cohort of 140 persons wearing removable maxillary polymethylamethacrylate prostheses. Data were obtained by (1) a questionnaire that included the identification of the subject, demographic and social data, medical history and behaviour; (2) intra-oral examination; (3) evaluation of the prosthesis; (4) microbiological examination; (5) yeast identification and analyses using Epi-info and the chi-square test. Results showed significant associations between DRS and yeasts, gender, age and alcohol consumption. We also found a significant relationship between the presence of yeasts and hyposalivation and decreased salivary pH. We found a highly significant difference between groups with and without DRS concerning the presence or absence of yeasts, regardless of the sample origin. Most cases of DRS showed the presence of Candida albicans. The results confirm a highly significant difference between groups with and without DRS concerning the presence or absence of yeasts.