Purpose To report molluscum contagiosum as the initial manifestation in acquired immunodeficiency syndrome (AIDS). Method Case report. A 34-year-old man was examined with atypical, extensive molluscum contagiosum of the eyelids. Results Biopsy of the lesions confirmed molluscum contagiosum, and a previously normal fundus now disclosed bilateral cotton wool spots and classic signs of cytomegalovirus retinitis in the left eye. Human immunodeficiency virus (HIV) antibody testing was positive. Conclusions Manifestation of atypical and extensive eyelid molluscum contagiosum may warrant additional history taking, comprehensive ophthalmic examination, including dilated ophthalmoscopic examination, and HIV testing.