This article presents a case of a patient diagnosed with an indolent form of chronic lymphocytic leukemia (CLL). He was being followed with close observation when he was diagnosed with Richter transformation, an aggressive lymphoma that develops from CLL. The development of Richter transformation carries a poor prognosis, in part, because of underlying molecular changes that give rise to the transformation. The prognosis also relates to the difficulty in the patient’s ability to receive chemotherapy because of poor marrow reserves from the disease or the residual impact of prior treatments. Advanced practice nurses who follow patients with CLL need to be aware of the potential for Richter transformation.