Glycophorins are an important group of red blood cell (RBC) transmembrane proteins. Monoclonal antibodies against GPA are employed in immunohistochemical staining during post-mortem examination: Through this method, it is possible to point out the RBC presence in tissues. This experimental study aims to investigate anti-GPA immunohistochemical staining in order to evaluate the vitality of the lesion from corpses in different decomposition state. Six cases were selected, analyzing autopsies’ documentation performed by the Institute of Legal Medicine of Rome in 2010–2018: four samples of fractured bones and three samples of soft tissues. For the control case, the fracture region of the femur was sampled. The results of the present study confirm the preliminary results of other studies, remarking the importance of the GPA immunohistochemical staining to highlight signs of survival. Moreover, this study suggests that the use of this technique should be routinely applied in cases of corpses with advanced putrefaction phenomena, even when the radiological investigation is performed, the macroscopic investigation is inconclusive, the H&E staining is not reliable. This experimental application demonstrated that the use of monoclonal antibody anti-human GPA on bone fractures and soft tissues could be important to verify whether the lesion is vital or not.