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Introduction Leptomeningeal disease (LMD) is a malignant spread to the meninges or cerebrospinal fluid (CSF). It is a rare, rapidly progressive and fatal condition that poses a diagnostic challenge due to varied neurological manifestations and low sensitivity diagnostic modalities. We present a case of LMD from malignant melanoma, diagnosed postmortem.Case A 63-year-old woman with well-controlled epilepsy and previously treated actinic keratosis presented with confusion, expressive aphasia, and seizures. MRI brain revealed leptomeningeal enhancement. CSF analysis observed reduced glucose (0.5 mmol/L), elevated protein (540 mg/L) and mononuclear pleocytosis (40 x10 6/L). Infective, cytological, autoimmune encephalitis, and antineuronal panels were negative, consistent with leptomeningeal disease. Whole-body CT was negative for malignancy. FDG PET detected uptake in the left axillary node and bowel, but biopsies were negative for malignancy. Repeat CSF yielded similar results. A leptomeningeal biopsy was inconclusive, and a second biopsy was declined by family due to rapid deterioration, leading to a decision for palliation. Postmortem histology revealed malignant melanoma.Conclusion LMD is an uncommon complication of malignancies, and its occurrence as the initial presentation of a new cancer diagnosis is even rarer. Although CSF cytology and brain biopsy remain the gold standard for diagnosis, their low diagnostic yield often necessitates repeated testing. Emerging approaches, including circulating tumour cells (CTCs) and (ctDNA), show promise but are clinically inaccessible. There is limited evidence for systemic therapies as LMD patients have historically been excluded from clinical trials due poor prognosis. This case highlights the need for improved diagnostics and therapies for LMD.