The authors of this article present a case of a woman diagnosed with a vaginal melanoma who developed paraneoplastic syndrome (PNS) soon after diagnosis. A review of the literature regarding PNSs in gynecological malignancies is also described in this article. To our knowledge, this is the first reported case of paraneoplastic cerebellar degeneration with opsoclonus myoclonus secondary to a vaginal melanoma. In addition, our patient had an unusually acute progression to pancerebellar symptoms over the course of 3 weeks. Her paraneoplastic symptoms improved significantly after partial resection of the melanoma.