<p>Retention and histological examination of major organs—particularly the heart and brain—are standard components of medico-legal autopsies aimed at determining the cause and manner of death. However, in France, the lack of standardized national guidelines has resulted in significant variability in these practices, raising both ethical and practical concerns. Families often express distress over the removal and destruction of symbolic organs, especially the heart and brain, for histological purposes. In this context, it is essential to avoid unnecessary organ retention, ensuring that medico-legal procedures remain ethically sound and sensitive to the needs of grieving families. This study retrospectively analyzed 142 autopsy cases performed at a French medico-legal institute between 2020 and 2022 to evaluate the diagnostic utility of histological sampling and the systematic retention of the entire heart and brain. Histology was found to contribute significantly to forensic conclusions in 49% of cases, although full organ retention was rarely indispensable. Notably, brain histology yielded diagnostic information in only 14% of cases, whereas heart histology was more informative, contributing in 44% of cases. Moreover, in most instances, the diagnostic value obtained from entire organs could have been achieved with a single tissue sample. These findings support a more selective approach to organ sampling, informed by macroscopic findings and clinical history, in order to fulfill diagnostic objectives while maintaining ethical integrity. The study highlights the pressing need for clear, evidence-based protocols in forensic histological practice to optimize resource utilization and respect the emotional concerns of bereaved families.</p>