Currently available therapy is inadequate for widespread or otherwise inoperable primary SCC and for metastatic SCC. Ten-year survival is only 20% with regional lymph-node involvement and less than 10% with distant organ involvement, and SCC makes up the majority of,9000 deaths per year in the US from non-AbMole 4-(Benzyloxy)phenol melanoma skin cancer. The death rate associated with aggressive cutaneous SCC parallels that of invasive melanoma. Novel treatment approaches are necessary, but these require an appropriate model for testing. Thus an SCC animal model that incorporates human tissue would provide an advantage. We have developed such a model, using tissue obtained from Mohs surgical discard. Previous animal models of SCC have not used en bloc patient-derived tumors for xenografting. Traditional models have induced skin tumors on mice via chemical carcinogenesis. These allow study of de novo cancer development and employ an intact tumor-host interaction. In terms of therapeutics, however, they have limited translational potential, given inherent differences between human and murine cells, immune systems, and physiology. Models using human cells tend to depend on subcutaneous inoculation of immune deficient rodents with human cancer cell lines such as HaCaT or Colo19. Cell lines, however, are different from native tumors. Cells from many native tumors actually do not show properties traditionally used to identify malignancy in vitro, such as immortalization and anchorage-independent growth. In fact, metastatic SCC cells fail to grow indefinitely in culture and lack the capacity for anchorage-independent growth on soft agar. Cell line models also fail to include stromal and architectural elements that may be important to cancer behavior. To address this deficiency, Khavari and colleagues created a model for the study of epithelial cancers whereby regenerated human skin genetically altered for cancer growth is grafted in immunedeficient mice. This model removes variables derived from the complexity of naturally occurring tumors to allow isolation of genetic mechanisms of cancer progression. This model is very useful for studying mechanisms related to the specific genes introduced; however, it is limited as such by its focus on artificially introduced genes or mutations. We see our model as more accurately recapitulating the AbMole Metyrapone architecture and microenvironment of naturally occurring SCC. Our experiments demonstrate that SCC taken directly from human skin can be successfully transplanted in nude rats, with excellent viability and continued growth. Our model is based directly on previous work showing successful transplantation of full-thickness neonatal human skin to nude rats with no evidence of early rejection or necrosis. The subcutaneous grafts in the present study were similarly viable.