Previous models to study the biology of melanoma have focused on individual factors, such as proliferative and invasive capacity, the microenvironment, angiogenesis, or systemic immune dysfunction. However, all of these factors contribute to melanoma progression in concert. One physiologic phenomenon that typifies the coordination of these processes is placental development, characterized by trophoblast proliferation, invasion into decidual tissues, angiogenesis, and transient organ systembased immune evasion. Herein, we explore expression of 34 proteins involved in placentation and determine their association with an established prognostic factor, tumor infiltrating lymphocytes (TILs), in a 118-patient tumor microarray (TMA). Melanoma expression of CD58 and galectin-9 independently predicted for a favorable prognosis. Patients could be categorized into three clusters based upon patterns of protein expression and TILs. Patients in Cluster 2 demonstrated frequent TILs and superior overall survival. Pathway enrichment using MetaCore™ from GeneGo, a Thompson Reuters company, showed that TIMP2 and CD44 were expressed more frequently within Cluster 2 patients, suggesting a potential association with TILs. A subset of melanoma patients appear to lack an organized immune response to the tumor, which portends a poor prognosis.