Background: Nail invasion by nondermatophytic molds (NDM) is considered uncommon with prevalence rates ranging from 1.45% to 17.6%. Objective: We report the clinical features and response to treatment of onychomycosis caused by these molds. Methods: From 1995 through 1998 we performed a mycologic study on 1548 patients affected by nail disorders, and we diagnosed 431 cases of onychomycosis including 59 cases of onychomycosis caused by molds. These include 17 patients with onychomycosis caused by Scopulariopsis brevicaulis , 26 patients with onychomycosis caused by Fusarium sp, 9 patients with onychomycosis caused by Acremonium sp, and 7 patients with onychomycosis caused by Aspergillus sp. Results: Onychomycosis caused by S brevicaulis , Fusarium sp, and Aspergillus sp may often be suspected by clinical examination. In fact 38 of 50 patients with onychomycosis resulting from these molds were affected by proximal subungual onychomycosis associated with inflammation of the proximal nailfold. In our experience mold onychomycosis is not significantly associated with systemic diseases or immunodepression. NDM are difficult to eradicate; by using and combining different treatments (systemic itraconazole, systemic terbinafine, topical terbinafine after nail plate avulsion, and ciclopirox nail lacquer) we were able to cure only 69.2% of patients with S brevicaulis onychomycosis, 71.4% of patients with Acremonium onychomycosis, and 40% of patients with Fusarium onychomycosis. Aspergillus onychomycosis, on the other hand, responded very well to therapy and all our patients were cured after systemic or topical treatment. Eradication of the mold produced a complete cure of the nail abnormalities in all the patients who responded to treatment. Conclusion: Clinical examination usually suggests diagnosis of onychomycosis resulting from NDM. Topical treatment can be more successful than systemic therapy to cure onychomycosis caused by S brevicaulis , Fusarium sp, and Acremonium sp. (J Am Acad Dermatol 2000;42:217-24.)