We present the clinical case of a 51-year-old male patient, affected by common variable immunodeficiency (CVID). In his history recurrent orbital cellulitis, exacerbation of chronic right dacryocystitis, lacrimal sac empyema with periodic episodes of dacryocutaneous fistolization. The coexistence of these particular immunological defects and the lack of literature about similar cases required an accurate evaluation of each step of the diagnostic and therapeutic approach. We performed an endoscopic endonasal dacryocystorhinostomy with “cold” instruments. No surgical complications were observed in the immediate postsurgical period. We balanced the necessity of a follow-up based on frequent office evaluation and the current pandemic emergency, in order to not expose the patient to an additional infectious risk. The discussion will focus on several aspects: the adequacy of radiological, the “cold” surgical technique, the choice of avoiding endocanalicular prostheses. We will discuss also about the use of oral and topical therapy, avoiding probable post-surgical infectious complications.