3D ex vivo tumor models are required which better replicate the microenvironment encountered by tumor cells in vivo. In this study, we applied bone tissue engineering culture techniques to develop an ex vivo 3D bone tumor model. Ewing sarcoma cells were cultured on poly(ε-caprolactone) (PCL) microfiber scaffolds, and cellular growth kinetics, morphology, and infiltration were assessed. Cell/scaffold constructs were then exposed to anticancer drugs for up to 16 days and drug response was compared to 2D controls. Ewing sarcoma cells were capable of attachment and proliferation on PCL scaffolds and dense scaffold infiltration up to 200 micrometers. Constructs could be maintained in culture for up to 32 days, and high density 3D cell growth conferred an increased resistance to anticancer drugs over 2D controls. This 3D tumor model shows potential for use in future studies of bone tumor biology, especially as it pertains to the development of new anticancer drugs.