Background and Objective Understanding the patient experience is important for identifying the unmet need in chronic lymphocytic leukemia. The current study aimed to develop a comprehensive chronic lymphocytic leukemia conceptual model. Methods The conceptual model was based on literature searches, review of chronic lymphocytic leukemia patient blogs/ forums, and interviews with five expert clinicians, with 20 patients who received at most one treatment (first line) for their chronic lymphocytic leukemia, and with 20 patients with relapsed or refractory chronic lymphocytic leukemia. De-identified interviews were transcribed, coded, and evaluated using qualitative data analysis software. Results Thirty-five prevalent chronic lymphocytic leukemia-related symptom and impact concepts were identified from literature searches, patient blogs/forums, and clinician interviews. Patient interviews confirmed the identified concepts and revealed five additional concepts. Fatigue-related sub-components were identified from how patients described their fatigue, covering symptoms (tiredness/need for sleep, lack of energy, weakness, cognitive fatigue), and impacts (decreased ability to maintain their social, familial, or professional role, decreased physical functioning, frustration). Three versions of the conceptual model were created: an overall model with all concepts; a model highlighting the most prominent concepts in first line; and a model highlighting the most prominent concepts in relapsed or refractory disease. Prominent concepts in both first line and relapsed or refractory disease were fatigue-related symptoms and impacts, muscle/joint aches, night sweats, bruising, fever, recurrent infections/illness, insomnia, decreased cognitive/emotional functioning, anxiety/worry, stress, depression, financial difficulty, and fear of death. Dyspnea and cough were prominent in first line only, and enlarged lymph nodes, headaches, pain/discomfort, weight loss, nausea/vomiting, and infusion reactions were prominent in relapsed or refractory disease only. Conclusions The results show that fatigue is a dominant issue affecting patients with chronic lymphocytic leukemia. The three versions of the conceptual model can help researchers to understand patients' unmet needs and guide the patient-reported outcome strategy for clinical trials.