Purpose <p>Guidelines recommend early palliative care for patients with cancer, including high grade glioma (HGG), but referrals to palliative care are often delayed. Our study aimed to describe characteristics and outcomes of patients with HGG with a first unscheduled hospitalization, and assess if it should trigger palliative care referral.</p> Methods <p>Retrospective study of medical oncology outpatients with HGG at a tertiary hospital, analyzing first unscheduled hospitalizations. Primary variable: Overall Survival (OS) after admission.</p> Results <p>133 HGG consecutive patients were referred to the medical oncology outpatient clinic. By the study’s end, 90% (<i>N</i> = 119) had died, with a median OS from diagnosis of 11 months (95% CI 10–14). Unscheduled hospitalizations occurred in 53% of patients (<i>N</i> = 71) and were associated to reduced median OS from diagnosis: 10.5 months vs. 14 months, HR (95% CI) = 1.9 (1.3–2.7), <i>p</i> = 0.0012. Mortality during hospitalization was 24% (<i>N</i> = 17). Median OS after admission was 2.5 months (95% CI 2–4). Poor ECOG performance status (<i>p</i> = 0.059), no prior cancer treatment (<i>p</i> = 0.0003), longer diagnosis-to-admission time (<i>p</i> = 0.0147), admission to acute palliative care unit (<i>p</i> = 0.0012), and discharge to Hospice (<i>p</i> &lt; 0.0001) associated with lower survival. Of admitted patients, palliative care assessed 39% (<i>N</i> = 28) during hospitalization, 28% (<i>N</i> = 20) before, and 24% (<i>N</i> = 17) after. Median OS after admission was shorter for those referred before/during hospitalization: 2 months vs. 7 months, HR (95% CI) = 0.4 (0.2–0.7), <i>p</i> = 0.0012.</p> Conclusion <p>The first unscheduled hospitalization in HGG patients could signal poor prognosis, yet palliative care referrals often occur late, highlighting missed opportunities for earlier intervention and suggesting unscheduled hospitalization as a potential trigger for referral.</p>