Emerging evidence has suggested that the capacity of a tumor to grow and propagate is dependent on a small subset of cells within a tumor: cancer stem cells. To test if cancer stem cells were present in human pancreatic cancer, the authors utilized a xenograft model in which primary human pancreatic adenocarcinomas were grown in immunodeficient NOD-SCID mice. They identified a highly tumorigenic subpopulation of pancreatic cancer cells expressing the cell surface markers CD44, CD24, and ESA. Pancreatic cancer cells with the CD44+CD24+ESA+phenotype (0.2-0.8% of all pancreatic cancer cells) had a 100-fold increased tumorigenic potential compared to nontumorigenic cells. The tumors derived from theCD44+CD24+ESA+ pancreatic cancer stem cells (right panels) were histologically similar and expressed similar differentiation markers (S100P and stratifin) as the primary human tumors from which they originated (left panels). The CD44+CD24+ESA+ pancreatic cancer cells demonstrated the stem cell properties of self-renewal, ability to produce differentiated progeny, and increased expression of the develop mental signaling molecule sonic hedgehog. Elucidation of the signaling pathways that regulate pancreatic cancer stem cells growth and survival may offer novel therapeutic approaches to treat pancreatic cancer. For details, see the article by Li et al. on page 1030 of this issue.