We reviewed the histopathological diagnosis of human cytomegalovirus (HCMV) and the pathology of HCMV infection in immunocompromised hosts. For histological diagnosis, routine staining of paraffin sections of formalin fixed tissue obtained at biopsy and autopsy is important to detect cytomegalic inclusion (owl's eye). For confirmation of HCMV diagnosis, immunohistological detection of immediate early and structural proteins of HCMV is valuable. Cytomegalic inclusion contains a Cowdry A inclusion consisting nucleocapsid and electron dense networks in the nucleus and sometime many dense bodies in the cytoplasm. In situ hybridization for viral transcripts and genome and immunohistological detection of immediate early proteins occasionally reveal HCMV-infected cells not showing cytomegalic inclusion. HCMV infections in immunocompromised hosts are not always associated with apparent clinical manifestations. Among these infections, gastrointestinal and retinal infections are frequently associated with serious outcomes.