Coccidioidomycosis is a fungal infection common in the southwestern United States that is caused by the endemic Coccidioides species of fungus. Coccidioidal infections are generally manifested as self-limited respiratory illnesses, but affected patients rarely present with coccidioidomycosis in extrapulmonary locations. Skin and soft-tissue coccidioidomycosis may occur in 15% to 67% of patients with disseminated infection. Skin manifestations of coccidioidomycosis can either be reactive rashes, such as erythema multiforme or erythema nodosum associated with primary pulmonary infection, or they can be the result of extrapulmonary dissemination of the infection to the skin. As many as 90% of persons with disseminated infection to the skin have other extrapulmonary sites of infection, and the presence of coccidioidal skin lesions should prompt an investigation for other extrapulmonary foci of infection. Lymph nodes are a common site of extrapulmonary infection. Nearly every organ system and soft-tissue have been described as infected with Coccididioides species, but subcutaneous abscesses, phlegmon, and sinus tracts are not uncommon and often are themselves the result of coccidioidal infection in neighboring lymph nodes, bones, or joints. A biopsy of the abnormal area is the most direct way to diagnose skin and soft-tissue lesions. Fluconazole and itraconazole are preferred therapeutic agents, and surgical intervention may be required as an adjunctive measure. This article reviews the types and locations of disseminated infections, as well as diagnostic studies and treatment of this difficult-to-treat manifestation of coccidioidomycosis.