When bone is exposed to the burial environment it may experience structural changes induced by multiple agents. The study of postmortem alterations is important to differentiate decomposition phenomena from normal physiological processes or pathological lesions, as well as to assess bone tissue quality. Microscopy is of great utility to evaluate the integrity of bone microstructure and it provides significant data on long-term bone decomposition. A total of 18 human bone sections (eight archeological and ten retrieved from an identified skeletal collection) were selected for analysis under plane light and polarized light. The aim of this exploratory study was to analyze the impact of diagenesis and taphonomy on the bone microstructure, as well as on the differential diagnosis of pathological conditions. The results showed that the microscopy approach to bone tissues contributed materially as an aid in the detailed description of the main diagenetic changes observed. It showed that gross inspection does not provide a realistic assessment of bone tissue preservation, which can impact in the characterization of lesions present and subsequent disease diagnosis. Therefore, researchers should continue to consider the application of histological techniques if the aim is to comprehend tissue integrity and its association with decomposition or disease.