Solid tumors are not simply clones of cancer cells. Instead, they are abnormal organs composed of multiple cell types and extracellular matrix. Some aspects of tumor development resemble processes seen in developing organs, whereas others are more akin to tissue remodeling. Some microenvironments, particularly those associated with tissue injury, are favorable for progression of mutant cells, whereas others restrict it. Cancer cells can also instruct surrounding tissues to undergo changes that promote malignancy. Understanding the complex ways in which cancer cells interact with their surroundings, both locally in the tumor organ and systemically in the body as a whole, has implications for effective cancer prevention and therapy.