Blastomycosis is the fungal disease caused by thermally dimorphic fungi in the genus Blastomyces, with B dermatitidis complex causing most cases. It is considered hyperendemic in areas adjacent to the Great Lakes and along the St. Lawrence, Mississippi, and Ohio rivers, but definitive geographic distribution of blastomycoses remains obscure. Clinical presentation is variable. Disseminated blastomycosis with extrapulmonary manifestations is more common in immunosuppressed individuals. Culture positivity is required for definitive diagnosis, but compatible histology is often sufficient for presumptive diagnosis and initiation of treatment. Treatment should be provided to all symptomatic cases to prevent progression or recurrence.