Background: Deep cutaneous fungal infections (DCFIs) are responsible for significant morbidity and mortality, particularly in immunocompromised patients. Although a direct correlation between histopathologic examination and culture is expected, discordant findings may be seen, presenting a unique diagnostic and therapeutic challenge. Objectives: We sought to determine the correlation between skin tissue cultures and histopathologic examination in patients with DCFI. Methods: This is a 10-year retrospective review (2003-2012) of patients with a diagnosis of DCFI seen at a single tertiary care institution. Tissue cultures and histopathologic findings were reviewed. Results: In 8 of 33 cases, fungal elements were seen on routine histopathologic sections but skin cultures were negative. Three of 8 of the discordant cases had concurrent positive non-skin tissue cultures that correlated with the pathology interpretation, and 3 of 8 patients in the discordant group died of systemic fungal infection. Limitations: This was a retrospective study design and a single tertiary care institution experience. Conclusions: The histopathologic interpretation of skin tissue specimens is critical for rapid and accurate diagnosis of DCFI. Despite the identification of fungal organisms on histopathologic assessment of skin tissue specimens, skin tissue culture may fail to show fungal growth. A diagnosis of a DCFI and initiation of appropriate treatment should always be considered in spite of discordant results.