The modern cancer system is composed of the comprehensive set of functions starting with population based cancer plans, cancer registries, public health functions, health system institutions that deliver all components of clinical care. Recent emphasis on health systems focuses on the population wide intervention. However, cancer centres, or cancer programs within health care institutions, are critical to the delivery of cancer care. Cancer centers are complex organizations that evolved over time to being able to provide a comprehensive set of interventions and act as champions for cancer prevention, treatment and supportive care, while at the same time promoting cancer research and education. Cancer centres may be supported in a country regardless of its resource level and they play an important role in advancing the clinical functions of cancer systems. In this chapter we describe a framework for a comprehensive cancer center which although focused on clinical care acts as an important anchor for a cancer system. The framework we propose outlines structures for clinical management, clinical services, core services, and system support with quality as an integrating theme. We describe the elements required for each clinical service to deliver care and the core services to support their functions. The significant benefits of comprehensive centers are identified.