This study determines the main routes by which cancer cells reach the pia-arachnoid in leptomeningeal carcinomatosis. Twenty-eight autopsy proven cases of pure carcinomatosis of the leptomeninges were reviewed and the collected data were compared to data derived from control groups of cases with lung or breast cancer, with and without central nervous system (CNS) parenchymal metastases. Pathologic and statistical evidence suggests that in most cases of breast or lung cancer pure leptomeningeal carcinomatosis is the result of cancer propagation from vertebral or paravertebral metastases; in most cases of primary gastrointestinal cancer metastasis to the leptomeninges takes place via perineural spaces; and in cases where deep CNS parenchymal metastases are present leptomeningeal carcinomatosis follows cancer metastasis via the arterial route. Direct spread of a primary cancer in proximity to the CNS accounts for a small proportion of cases of cancerous invasion of the pia-arachnoid. It is not certain if metastasis can take place via the choroid plexus or meningeal arteries.