Untransformed human cells exhibit normal cellular behavior and mediate their growth and proliferation via interplay between environmental nutrients, growth factor signaling, and cell density. As cell density increases and the culture becomes confluent, they initiate cell cycle arrest and downregulate proliferation and mitogen signaling pathways regardless of external factors or cellular metabolism. This property is known as contact inhibition of proliferation and is essential to proper embryonic development, as well as tissue repair, differentiation, and morphogenesis. Cancerous cells typically lose this property and thus divide and grow over each other in an uncontrolled manner even when in contact with neighbouring cells. This results in the invasion of surrounding tissues, their metastasis to nearby organs, and eventually tumorigenesis. Cells of naked mole rats, a species in which cancer has never observed, show hypersensitivity to contact inhibition. This finding may provide a clue to cancer resistance. Furthermore, recent studies have further revealed some mechanisms of contact inhibition of proliferation and its potential implications in cancer therapy.