Background: Isolated central nervous system lymphomas (CNS-L) has non-specific clinical presentations causing delays in diagnosis and treatment. This retrospective case series aims to characterize these challenges in the inpatient setting. Methods: Chart review of biopsy-proven CNS-L cases (n=10) presenting to Vancouver General Hospital from 2018-2020: diffuse (8/10) and intravascular (2/10) large B-cell lymphomas were included. Results: Median age was 69 years (31-83); 50% were female; 9/10 immunocompetent, 1/10 had well-controlled HIV. Neurologic symptoms at presentation: ataxia (7/10), paresis (4/10), dysphagia (4/10), dysarthria (2/10), and cognitive decline (4/10). Median time from symptom onset to admission with paresis, ataxia, dysphagia, or dysarthria was 3 days (1-14), compared to 84 days (28-384) with transient/vague symptoms. Median time from admission to biopsy was 25 days (5-148). 4/10 received steroid prior to biopsy. 1/10 had solitary lesion on MRI, 8/10 had ≥2 lesions. Diagnosed on lumbar puncture (0/10), skin biopsy (1/10), vitreous biopsy (1/10), brain biopsy (8/10), autopsy (1/10). 4/10 survived, 6/10 died; median time from admission to mortality was 133 days (61-342). Conclusions: Many factors lead to delays in diagnosis and treatment of CNS-L, including non-specific clinical presentations and time to brain biopsy for definitive diagnosis. Earlier recognition and reducing biopsy delays may help achieve earlier diagnosis.