Background: Patients with the acquired immune deficiency syndrome are at risk for the development of multiple lesions of Molluscum contagiosum on the eyelids. In this setting, traditional methods of treatment frequently are ineffective and pose risks to the patient as well as to the treating physician. Methods: A technique was developed that combined lidocaine/prilocaine topical anesthesia with hyperfocal cryotherapy. Twelve patients with multiple M. contagiosum lesions of the eyelids were treated. Initially, two methods were used: one application for 30 seconds or two applications for 20 seconds. Results: Lesions treated with two 20-second applications regressed. Most of those lesions treated for 30 seconds regressed. No scarring, lash complications, ptosis, or damage to the underlying cornea or deeper ocular structures was observed in any patient. Conclusions: Hyperfocal cryotherapy is an effective therapy for multiple M. contagiosum lesions of the periorbital region, posing minimal risk to the patient and physician. It is particularly useful in patients who are positive for the human immunodeficiency virus, who frequently have multiple lesions, are likely to have recurrent disease, and who pose risks of disease transmission to the medical personnel caring for them. © 1995, American Academy of Ophthalmology, Inc. All rights reserved.