The capacity to induce neoplasia in human tissue in the laboratory has recently provided a new platform for cancer research. Malignant conversion can be achieved in vivo by expressing genes of interest in human tissue that has been regenerated on immune-deficient mice. Induction of cancer in regenerated human skin recapitulates the three-dimensional architecture, tissue polarity, basement membrane structure, extracellular matrix, oncogene signalling and therapeutic target proteins found in intact human skin in vivo. Human-tissue cancer models therefore provide an opportunity to elucidate fundamental cancer mechanisms, to assess the oncogenic potency of mutations associated with specific human cancers and to develop new cancer therapies.