Introduction: A blended radiation therapy course was developed to meet continuing education needs of nurses working with patients diagnosed with cancer in diverse health care settings. The purpose of this paper is to describe the design, development, and evaluation of an innovative blended radiation therapy course including eLearning modules using virtual animated character guides, an independent self-managed project, and a one-day face-to-face symposium. Methods: A pre/post-test group design was employed using standardized program evaluation measures. Participant data included self-reported confidence in knowledge of radiation therapy. Additional evaluation included assessment of the virtual animated character guides, and open-ended feedback of the overall course and areas of improvement. Results: A total of 51 participants enrolled in two separate iterations of the course with a 71% response rate. In Group A (n = 17) statistically significant improvements were identified at post-test in self-perceived confidence levels in knowledge for 11 of 12 radiation therapy domains (p < .05). In Group B (n = 19), statistically significant improvements in self-perceived confidence levels in knowledge were identified in all domains (p < .05). Discussion/Conclusions: The course provided a learning environment that drew on a variety of technologies and delivery methods. The improved confidence levels in knowledge may enhance individual nurses' ability to address the needs of patients undergoing radiation therapy. Interactivities, virtual animated character guides, discussion forums, the project assignment, and the symposium were activities perceived to be conducive to learning. Further evaluation may elucidate if confidence level in knowledge gained from the course was assimilated into practice and improved information and education needs of patients.