The incidence of leptomeningeal metastases (LM) in patients with breast cancer (BC) is increasing as a result of increased screening and improved patient survival. However, the median survival time after diagnosis of LM is between 5 weeks (without any treatment) and 5 months (for aggressively treated patients). In an attempt to identify clinicopathological risk factors for LM, we carried out a case-control study of 100 women with BC. Fifty patients with BC and LM were enrolled and an additional 50 patients with BC and no CNS metastases including leptomeningeal spread were selected as controls. Patients who had developed LM were selected between December 2006 and August 2008. The control group was matched for: age at diagnosis, year of diagnosis, and initiation of chemotherapy at BC diagnosis. The ILC type (P = 0.03), ER-negative (P = 0.01) and PR-negative status (P = 0.03), and initial M+ status at BC diagnosis (P = 0.008) tended to be more frequent in LM patients. These characteristics should lead to early appropriate assessments being performed in this targeted population when a neurological complaint appears, in order to detect LM as soon as possible.