--- - |2+ Abstract Objective Rare cancers are a heterogeneous group of conditions that can be associated with emotional and physical impairments. In view of the dearth of research in this area, we investigated the quality of life and prevalence of distress in a cohort of patients diagnosed with a rare cancer, classified by the RARECARE definition. Methods A cohort of rare cancer patients, treated in a Brazilian public cancer center, was assessed for distress (Distress Thermometer), anxiety/depression (Hospital Anxiety and Depression Scale), and quality of life (Functional Assessment of Cancer Therapy‐General Version). Descriptive statistics were generated, and multivariate analyses were used to identify factors associated with distress, anxiety/depression, and quality of life. Results A total of 137 patients (52.6% male, mean age of 50 years; range 18‐90) were identified. Nearly half (49.6%) of patients reported high levels of distress, with 19.7% endorsing anxiety and 15.3% depression. In multivariate analysis, demographic and clinical variables associated with worse psychosocial outcomes included younger age (P < 0.05), female gender (P < 0.01), advanced disease stage (P < 0.01), and engagement in active therapy (P < 0.05). Conclusions Patients diagnosed with rare cancer reported poorer psychosocial outcomes and impaired quality of life when compared to the general population of cancer patients. Certain demographic groups (eg, women and younger patients) may benefit from targeted psychosocial interventions. - Psycho-Oncology, EarlyView.