<p>There is a known association between nevus of Ota and melanomas involving the brain parenchyma and/or the meninges. We present the unusual case of a 32-year-old African-American female with a nevus of Ota and a contralateral parenchymal, primary CNS melanoma. We discuss the unique features of this case and provide a brief review of the literature regarding nevi of Ota and associated CNS melanoma. Our patient is a 32 year-old, African-American female with a left-sided nevus of Ota who presented with a three month history of headaches and paresthesias involving her left face and arm. An MRI of the brain revealed a hemorrhagic mass in the right temporal lobe, which, after craniotomy, was determined to be a melanoma. Extensive imaging, ophthamologic examination and full-body skin examination revealed no other foci of melanoma. To our knowlege, this is the only case of a nevus of Ota associated with contralateral parenchymal melanoma in an African-American patient. The association of contralateral parenchymal primary CNS melanoma with nevus of Ota is extremely unusual. Futhermore, despite the association of nevus of Ota with CNS melanoma, the literature does not support routine screening of patients with nevus of Ota for CNS melanoma with imaging modalities. </p>