Madagascar hissing cockroaches (MHC, Gromphadorhina portentosa) are members of the Blaberidae (giant cockroaches) family of the Insecta class. They are native to the African island of Madagascar where they live within leaf litter on the rainforest floor. Due to their large size, relative tameness, and general easy keeping, they have become popular in classrooms, zoological collections, museums, research laboratories, and as private exotic pets; however, descriptions of diseases of MHC in the literature are rare. The objective of this study is to describe and characterize postmortem histological findings in 18 captive MHC from a single zoological collection. In this retrospective study, 18 (4 females and 14 males) adult MHC necropsies were submitted to Northwest ZooPath between 2016 and 2020 for evaluation. The main organs with histological lesions were chitinous gut (foregut and/or hindgut; n = 17), tracheae (n = 15), fat body (n = 14), ventriculus (midgut) (n = 13), body wall (n = 12), Malpighian tubules (n = 12), and hemolymphatic sinuses (n = 12). All animals had inflammatory lesions affecting various organs. Inflammatory lesions typically consisted of aggregates of hemocytes with variable amounts of melanization and/or encapsulation. Bacterial, fungal, and parasitic infections were common and variably associated with hemocytic inflammation. Many of these organisms may represent symbiotic organisms of the MHC that cause opportunistic infections. This study contributes to the current knowledge of pathological findings and disease response of MHC and reviews diseases reported in multiple cockroach species.