A major children's cancer and hematology center established a Quality Transformation (QT) Core to develop and monitor empirical outcomes that demonstrate excellence in clinical care. The QT Core, based on the Institute of Medicine's domains of quality health care, aims to ensure that care is safe, effective, patient centered, timely, efficient, and equitable. Specific goals for the first year of the QT Core were to develop a team of improvement science experts, engage faculty and staff in QT initiatives, promote accountability for excellence in clinical care, and establish specific metrics to evaluate process, structure, and outcomes for QT Core projects. The purpose of this article is to discuss the successful development of a quality transformation core within a pediatric subspecialty and demonstrate the principles of improvement science through an actual quality transformation project designed to implement an evidence-based guideline for procedural sedation for children with cancer. The QT Core within this subspecialty was founded on principles of successful transformation of patient care that includes motivation to change, leaders committed to quality, active engagement of staff in meaningful problem-solving initiatives, alignment with organization goals with resource allocation, and integration to bridge boundaries throughout an organization. These key principles are demonstrated through the discussion of the development of the QT Core and implementation of an evidence-based procedure sedation guideline. Pediatric and pediatric subspecialty groups can be on the forefront of national initiatives that promote quality health care, exemplified by the QT Core developed within the cancer and hematology center.