Cutaneous lesions in patients with systemic lupus erythematosus (SLE) represent diagnostic challenges. Opportunistic infections should be considered when lupus patients are on immunosuppressive therapy and other causes, such as disease activity, are less likely to explain the skin lesions. Within the spectrum of skin opportunistic infections that might occur in SLE patients, Blastomyces dermatitidis should be suspected when acid-fast positive material with no bacilliform organisms is seen on Ziehl-Nielsen skin biopsy preparations. In this study, we describe one patient with SLE on immunosuppressive therapy, who developed cutaneous blastomycosis despite living in a non-endemic area. Because of lack of awareness about this association and misinterpretation of the skin biopsy results, the diagnosis of atypical mycobacterial infection was initially considered. Subsequent proper tissue staining and interpretation revealed the correct diagnosis of disseminated cutaneous blastomycosis. This description represents the first report of this rare opportunistic skin infection in SLE, illustrating the importance of performing correct preparation and elucidation of the skin biopsy to avoid misdiagnosis and treatment delay.