The study introduces a novel approach to cancer research using topobiologically complex mini-colons capable of undergoing tumorigenesis ex vivo. Traditional organoid systems have limitations in capturing the evolutionary process of cancer development, necessitating the use of animal models. The developed mini-colons integrate microfabrication, optogenetic, and tissue engineering techniques to allow spatiotemporal control of tumorigenic transformation through blue-light exposure. These mini-colons enable real-time tracking of emergent colon tumors at single-cell resolution for several weeks. They exhibit rich intratumoral and intertumoral diversity, recapitulating key pathophysiological hallmarks of colorectal tumors in vivo. This system offers a platform for cancer initiation research outside living organisms, providing insights into tumorigenic determinants and pharmacological opportunities.