PURPOSE: To describe a case of conjunctival squamous cell carcinoma in situ that was successfully treated with adjunctive topical cidofovir. DESIGN: Interventional case report. METHODS: A 52-year-old woman presented with a diagnosis of diffuse conjunctival papillomatosis in the right eye. She underwent conjunctival biopsy followed by a 6-week course of cidofovir eyedrops (2.5 mg/ml). RESULTS: The biopsy specimen demonstrated squamous cell carcinoma in situ. After this biopsy and treatment with cidofovir, the mass regressed into a small vascular tuft, which was excised and treated with cryotherapy. Six months after cidofovir treatment, the patient developed cicatricial changes of the inferior punctum. No recurrence of the squamous cell carcinoma has occurred in 24 months of follow-up. CONCLUSION: Cidofovir has shown effectiveness in the treatment of neoplastic lesions involving various mucus membrane sites. This antiviral drug may be a valuable addition to our treatment armamentarium for patients with squamous cell carcinoma in situ of the conjunctiva. The possible relationship between topical cidofovir and cicatricial changes of the lacrimal system cannot be determined from this isolated report, but further investigation is indicated.