Background The re-emergence of Monkeypox (MPX) and its related ophthalmic disease represent a clinical challenge in the initial stages because of the presence of lesions like those caused by varicella zoster, syphilis, and other infections due to other poxviruses. Human Immunodeficiency Virus (HIV) infection and secondary immunodepression raise the risk of severe and prolonged disease. Purpose We present the case of a young immunosuppressed male patient with MPX, who presented with multiple skin lesions, also including risky ophthalmological manifestations due to extensive eyelid involvement. Conclusions We describe a novel form of late-onset conjunctivitis and eyelid lesions, without active extraocular disease, highlighting the heterogeneous behavior of the new clinical form of MPX, that exhibits a wide spectrum of lesions in different stages of evolution.