ABSTRACT Introduction: Leptomeningeal carcinomatosis (LC) is diagnosed in 4-15% of cancer patients, and most cases (70%) are in the advanced phase of the disease. In only 5-10% of patients with LC, it is the initial manifestation of cancer. Case report: We present a case of a 46-year-old man with leptomeningeal carcinomatosis as the first manifestation of type B high-grade lymphoma. Cerebrospinal fluid (CSF) showed pleocytosis with a predominance of mononuclear cells, hyperproteinorrhachia, and glucose consumption. CSF cytology was negative for malignant cells in two samples. Magnetic resonance imaging and CSF flow cytometry gave the diagnosis. Discussion: LC is a diagnostic challenge. Differential diagnosis arises with infectious processes (tuberculosis) and autoimmune diseases. In cerebrospinal fluid, flow cytometry (FCM) has a higher sensitivity than cytology for the diagnosis of LC.