Acute dacryocystitis often results from the acute attack exacerbation of chronic dacryocystitis. Typical symptoms include those of chronic dacryocystitis, such as persistent tearing, increased abnormal secretions, as well secondary manifestations of acute dacryocystitis like redness, swelling, heat and pain in the lacrimal sac area, which are predominantly unilateral. Chronic lymphocytic leukemia (CLL) is a malignant blood disorder originating from hematopoietic tissue. On the surface, these two diseases do not appear to be directly related in terms of pathophysiology. This study reported a case of CLL presenting with acute dacryocystitis as the initial symptom. The patient exhibited signs of acute dacryocystitis in both eyes, and was subsequently diagnosed with CLL following a systemic examination. Meanwhile, a review of the relevant literature revealed similar reports. However, in one instance, acute dacryocystitis in children with leukemia appeared as the first sign of acute leukemia itself, while in another, acute dacryocystitis was diagnosed as CLL by pathological biopsy after dacryocystectomy. At present, there have been no report of significant remission of acute dacryocystitis following conservative treatment for CLL. The occurrence of this condition may be related to the changes in lacrimal drainage-associated lymphoid tissue (LDALT). As a part of the mucosal immune system, LDALT can guide CLL cells to migrate and colonize within it, thereby disrupting the local immune microenvironment, interfering with the immune balance of the lacrimal passage, inhibiting the function of normal immune cells, promoting abnormal lymphocyte proliferation in the nasolacrimal duct, and ultimately leading to impaired drainage of the lacrimal passage system. Additionally, the systemic immunosuppressive state induced by CLL reduces the body’s overall anti-infective capacity, increasing the risk of dacryocystal infection and ultimately contributing to the onset and progression of acute dacryocystitis. Through a comprehensive analysis of the potential pathogenesis of this case, we aim to explore its implications for clinical diagnosis and treatment.