Abstract In the field of oncology research, next-generation sequencing has contributed significantly to the discovery of DNA mutations associated with diagnosis and prognosis. It also aids in the development of targeted therapies to specific mutations and the rise of personalized medicine. As part of molecular diagnostics in cancer patients, analysis by next-generation sequencing is becoming part of routine clinical practice. The introduction of this complex technology in a healthcare system comes with multiple challenges and requires a clear action plan. Such an action plan, as outlined in this paper, was developed in Belgium and includes steps in ensuring the quality and indications of NGS testing, installing data registration and tackling ethical issues. A final step is to perform a pilot study to control the access, quality, harmonization and expertise in DNA testing. This action plan can serve as a guide for similar initiatives by other countries to facilitate NGS implementation in clinical practice.