In this article, we evaluate the association between the Fort King George "skull" and two Franciscans who were killed during a Guale revolt in 1597 and whose remains were never recovered (Pedro de Corpa and Francisco de Veráscola). The history and historiography of the revolt is summarized to generate a forensic profile for the individuals. The calvaria is described in terms of preservation, taphonomy, possible trauma, age, and sex. Because these factors are consistent with the individuals in question, population affinity is assessed using comparative craniometric analysis. In response to recent criticism of the typological nature of forensic population affinity assessment, we use a population specific approach, as advocated by Alice Brues (1992). Archaeological and historical data inform the occupation history of the site, and data from those specific populations are used in the comparative analysis. Results of linear discriminant function analysis indicate a low probability that the calvaria is a Guale (the precontact inhabitants of southeastern Georgia) or an individual of African descent. Comparison among European and Euro-American populations indicated poor discriminatory resolution; however, the closest match suggests a New World affinity rather than an Old World English, Scottish, or Iberian affinity for the specimen. Future analyses that will provide greater resolution about the identity of the calvaria are outlined. The case highlights the unique challenges of historical forensics cases relative to those of traditional jurisprudence, as well as the potential for using historiography to overcome those challenges in future analyses.