Human tissue specimens are critical reagents in the diagnosis of disease and biomedical research. Tissues experience rapid degradation immediately after ligation from their blood supply. A variety of processing techniques are employed to prevent the degradation of tissue samples, principally chemical fixation and thermal processing. The success of processing techniques is measured by the preservation of tissue morphology, as well as the critical biomarkers. In preservation of tissue specimens, formaldehyde is the most widely used fixative that maintains tissue morphology. However, the cross-links resulting from chemical interactions between formaldehyde and biomolecules in the specimens introduce difficulties in detection and extraction of antigens for analysis. Alternative processing methods, such as chemical fixation (e.g., alcohol-based) or thermal processing (e.g., freezing) help avoid the loss of antigenicity due to cross-linking, but introduce morphological artifacts. In this article, we review methods of processing of fresh tissue samples, as well as the effects of these procedures on morphology and antigenicity of the preserved tissues as assessed by histology, immunohistochemistry, proteomics, and genomics.