Background and objective Acute dacryocystitis is an atypical and rare manifestation of pediatric mononucleosis still widely underdiagnosed in clinical practice. We report this rare condition and describe challenges in its diagnosis and treatment on the basis of a presented case. Case presentation A 6-year-old Caucasian girl without any ophthalmic history was admitted for right preseptal cellulitis requiring intravenous antibiotic therapy. During hospitalization, she developed a fluctuating lump in the nasolacrimal region which resembled an abscess, both clinically and radiologically. There was no spontaneous purulent discharge. Serology was positive for acute mononucleosis and Epstein–Barr virus-related dacryocystitis was diagnosed. Following multidisciplinary discussion, she was treated conservatively with digital lacrimal sac massages and intravenous antibiotic therapy with an excellent outcome. Discussion This rare form of Epstein–Barr virus is poorly documented in the literature, and thus barely known. As initial symptoms are nonspecific (rhinitis, fever, eyelid edema and erythema lack of purulent discharge, and moderate bilateral cervical lymphadenopathy), diagnosis is often difficult. Nevertheless, differentiating between dacryocystitis and abscess is crucial to select the appropriate treatment and avoid unnecessary, potentially harmful surgery. Conservative management of dacryocystitis appears to be the gold standard of treatment. Conclusion Acute dacryocystitis in children free of ophthalmic history should raise suspicion of primary Epstein–Barr virus infection. With conservative treatment, prognosis appears to be excellent; therefore, surgery should be avoided as much as possible.