Isolated blastomycosis hand infections are extremely rare, and are often clinically unsuspected, leading to delays in clinical diagnosis. Conclusive diagnosis often necessitates fungal cultures and histopathological demonstration of budding yeasts in tissues. In this report, we describe the rare occurrence of isolated blastomycotic hand infection, without any other organ involvement, in a 42-year-old male patient. Analyzing tissue specimens with frozen section has been shown in the past to demonstrate granulomatous inflammation and yeast forms of the organism; however, as demonstrated in this patient, the presence of pseudoepitheliomatous cells may deceptively appear as malignant, causing substantial concern and anxiety.