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Diffuse midline glioma with H3 K27M mutation is a new tumor entity from 2016 which is highly aggressive and classified as a WHO Grade IV tumor regardless of histopathologic features. We report a case of a 40-year-old male with diffuse midline glioma with pathology confirmation of histone H3 K27M mutation presenting predominately with subacute lower motor neuron syndrome mimicking long segmental myelitis. Our case will remind physicians that diffuse midline gliomas with H3 K27M mutation should be considered for differential diagnosis when there is long segmental spinal cord lesion. Careful evaluation should be done when there is atypical clinical manifestation.