Stem cells have been highlighted for a possible clinical trial in amyotrophic lateral sclerosis (ALS), and have been employed in SOD1 mice and ALS patients. Human trials for stem cell transplantations have used intrathecal route by lumbar puncture. However, stem cells introduced via lumbar injection would tend to sink downwards rather than ascending to the brain and cervical and thoracic spinal cord. Therefore, we adopted for intraventricular injection via an Ommaya reservoir, and wished to test the practicality of intraventricular stem cell injection in ALS. In the case presented autologous mesenchymal stromal cells (MSCs) were isolated from the bone marrow of a male patient with ALS who underwent insertion of an Ommaya reservoir. Expanded MSCs (hBM-MSCs: dose of 1 X 106 cells/kg) were suspended in autologous CSF and directly transplanted into the ALS patient's lateral ventricle via the Ommaya reservoir. Clinical, laboratory, and radiographic evaluation of the patient revealed no serious adverse effects related to the stem cell therapy. Intraventricular injection with an optimized number of cells is safe, and is a potential route for stem cell therapy in patients with ALS. Intraventricular injection via an Ommaya reservoir makes repetitive injection of stem cells easy and reliable even in far advanced ALS patients.