Neurofibromatosis type 2 (NF2) is an autosomal dominant disease of the nervous system characterized by multiple schwannomas. The NF2 gene product, termed schwannomin or merlin, was hypothesized to function as a cytoskeleton-membrane linking protein due to homology to members of the protein 4.1 superfamily and to function as a tumor suppressor. We isolated and characterized pure Schwann cell cultures from schwannomas derived from neurofibromatosis 2 patients with identified germline mutations and loss of heterozygosity. We describe striking differences between NF2 and control Schwann cells in morphology, cell-cell contacts, and growth. NF2 Schwann cells form multiple long processes with filopodial and lamellopodial extensions. NF2 Schwann cells lack contact inhibition, grow in multiple layers, and show a higher proliferation rate than control cells. For the first time Schwann cells derived from patients with the NF2 genotype were cultured and characterized in vitro. These cultures are highly valuable for investigating the effects of NF2 mutations and the development of therapies.