Purpose of Review: The classical diagnostic principles for applying histopathology for the diagnosis of invasive fungal diseases are reviewed. Although several new molecular based techniques have recently been developed, the histopathological identification of fungal elements together with a typical tissue reaction remains the golden standard for stating a diagnosis of invasive mycosis. Therefore, and due to the risk of false negative and false positive results obtained from cultivation as well as the non-culture based diagnostic test for invasive fungal infections, an examination should always complement histopathology in the diagnosis of invasive fungal diseases. Recent Findings: The application of molecular in situ identification techniques, i.e., immunohistochemistry and in situ hybridization, for morphologically observed fungal elements in tissue sections, has indeed improved the diagnostic accuracy of histopathology for the diagnosis of invasive fungal diseases. Summary: Because the specific molecular techniques applied in the histopathological diagnosis of invasive mycoses are directed toward specific targets, the panel of specific immunoglobulins/probes to be used on tissue sections should be directed from the histomorphology of the fungal elements as detected by conventional histopathological methods.