Proximal subungual onychomycosis (PSO) is a rare subtype of onychomycosis with a clinical presentation characterized by proximal leukonychia in the lunular area of the nail. PSO is associated with immunosuppression and regarded a sign of Human Immunodeficiency Virus (HIV) infection when caused by Trichophyton (T.) rubrum. We present two cases of PSO caused by T. rubrum developed during treatment with TNF-α inhibitors combined with methotrexate (MTX).