Nature Cancer, Published online: 03 April 2026; doi:10.1038/s43018-026-01138-xLeptomeningeal metastases are a devastating complication of solid tumors; how this niche becomes pro-metastatic remains poorly understood. A study now reveals that tumor cells prime a pre-metastatic niche within the leptomeninges via exosome-derived 5-HIAA, triggering vascular leakiness and accumulation of disseminated tumor cells.