Objective: We aimed to develop a telehealth network to deliver postdiagnosis cancer care clinical services and education to American Indian and Alaska Native patients, their families, and their healthcare providers. We also sought to identify the challenges and opportunities of implementing such a telehealth-based application for this rural and underserved population. Materials and Methods: We followed a participatory formative evaluation approach to engage all stakeholders in the telehealth network design and implementation. This approach allowed us to identify and address technical and infrastructure barriers, lack of previous experience with telehealth, and political, legal, and historical challenges. Results: Between September 2006 and August 2009, nine tribal clinics in Washington and 26 clinical sites in Alaska had participated in the telehealth network activities. Network programming included cancer education presentations, case conferences, and cancer survivor support groups. Twenty-seven cancer education presentations were held, with a total provider attendance of 369. Forty-four case conferences were held, with a total of 129 cases discussed. In total, 513 patient encounters took place. Keys to success included gaining provider and community acceptance, working closely with respected tribal members, understanding tribal sovereignty and governance, and working in partnership with cultural liaisons. Conclusion: The telehealth network exceeded expectations in terms of the number of participating sites and the number of patients served. Following a participatory formative evaluation approach contributed to the success of this telehealth network and demonstrated the importance of community involvement in all stages of telehealth system design and implementation.