Increased awareness of cancer as a health crisis facing less developed healthcare systems has led to recent calls for increased investment in cancer care infrastructure in low resource settings. However, operational descriptions of well-functioning cancer care systems in resource-constrained settings are limited. AMPATH-Oncology is the result of collaboration between North American, European, and Kenyan partners to develop a comprehensive cancer care model that supports screening services, cancer treatment, and palliative care. This article describes the approach taken by the AMPATH-Oncology program to deliver cancer care in a resource-constrained setting. A review of other ‘high-income – low-income’ collaborative models identifies successful strategies to implement cancer care in low resource environments.